Prevention of Neural Tube Defects by Periconceptional Folic Acid Supplementation in
Europe
(Updated version December 2009)
EUROCAT Central Registry Room 15E12, University of Ulster
Newtownabbey, Co Antrim Northern Ireland, BT37 0QB
Tel: +44 (0)28 90366639 Fax: +44 (0)28 90368341
Email: [email protected] Wesite: www.eurocat.ulster.ac.uk
EUROCAT receives funding from the European Union, in the framework of the Public Health Programme WHO Collaborating Centre for the Epidemiology Surveillance of Congenital Anomalies
2
This report was compiled by the EUROCAT Folic Acid Working Group:
Coordinators: Hermien de Walle and Lenore Abramsky
Part I: Hermien de Walle and Lenore Abramsky
Part II: Lenore Abramsky, Marie-Claude Addor, Emmanuelle Amar, Andre
Baguette, Ingeborg Barisic, Andrea Berghold, Sebastiano Bianca,
Fabrizio Bianchi, Paula Braz, Elisa Calzolari, Marianne Christiansen, Anne
Kjersti Daltveit , Hermien De Walle, Carlos Dias, Grace Edwards, Monika
Eichholzer, Miriam Gatt, Blanca Gener, Yves Gillerot, Romana Gjergja,
Janine Goujard, Martin Haeusler, Anna Latos-Bielenska, Bob McDonnell,
Vera Nelen, Amanda Neville, Ksenija Ogrizek Pelkic, Simone Poetzsch,
Isabel Portillo, Annukka Ritvanen, Elizabeth Robert-Gnansia, Janos
Sandor, G Scarano, Volker Steinbicker (emeritus), Romano Tenconi,
Visnja Tokic
Registry leaders of registries contributing neural tube defect data – Lenore
Abramsky, Marie-Claude Addor, Emmanuelle Amar, Ingeborg Barisic, Sebastiano
Bianca, Fabrizio Bianchi, Patricia Boyd, Elisa Calzolari, Catherine de Vigan, Hermien
de Walle, Elisabeth Draper, Grace Edwards, Maria Feijoo, Christine Francannet,
Ester Garne,Miriam Gatt, Yves Gillerot, Martin Haeusler, Lorentz Irgens, Anna Latos-
Bielenska, David Lillis, Mary O’Mahony, Maria-Luisa Martinez-Frias, Bob McDonnell,
Carmen Mosquera-Tenreiro, Vera Nelen, Annette Queisser-Luft, Simone Poetzsch,
Isabel Portillo, Judith Rankin, Annukka Ritvanen, Elisabeth Robert, Joaquin
Salvador, Janos Sandor, Gioacchino Scarano, Volker Steinbicker, Claude Stoll,
David Stone, Romano Tenconi, David Tucker, and Diana Wellesley.
We thank Barbara Norton for secretarial support. We thank Nicky Armstrong, Araceli
Busby, Helen Dolk and Maria Loane for their contribution to a previous report which
is updated here. We thank Ruth Greenlees for providing data from the EUROCAT
database.
3
We thank the registry staff and health professionals across Europe who provided
data on neural tube defects for this Report.
EUROCAT is supported by the Public Health Programme of the European
Commission
4
Table of Contents Recommendations Executive Summary Part I: Overview of Neural Tube Defects 1. Introduction 2. The Public Health Response to Evidence Concerning the Protective Effect of Folic Acid
2.1 Periconceptional Folic Acid Policies in European Countries
2.2 Uptake of Recommendations to take Folic Acid Supplements
2.3 Monitoring of intake of folic acid
2.4 Fortification of Food with Folic Acid
3. NTD Prevalence Rates in Europe 1980-2007 3.1 Methods
3.2 Results
3.3 Discussion
4. Conclusions 5. References
5
Part II: Country-specific Chapters Austria Belgium Croatia Denmark Finland France Germany Hungary
Ireland Italy Malta Netherlands Norway Poland Portugal
Slovenia Spain
Sweden Switzerland Ukraine
United Kingdom
6
Recommendations
1) European countries could prevent most neural tube defects in planned
pregnancies by putting in place an official policy recommending
periconceptional folic acid supplementation and taking steps to ensure that the
population are aware of the benefits of supplementation and the importance of
starting supplementation before conception.
2) European countries should review their policies regarding folic acid fortification
and supplementation taking into account available information on benefits and
hazards of both. They should pay special attention to results of studies done
post mandatory fortification in countries that have introduced it.
3) As many pregnancies are unplanned, European countries could achieve more
effective prevention of neural tube defects by additionally introducing
fortification of a staple food with folic acid. The particular objectives of this
policy would be preventing neural tube defects among women who do not plan
their pregnancy, and reducing socio-economic inequalities in neural tube
defect prevalence.
4) Health effects of supplementation and fortification should be monitored, and
policies should be reviewed periodically in light of the findings.
5) The European population should be covered by high quality congenital
malformation registers which collect information about affected pregnancies
(livebirths, stillbirths and terminations for fetal abnormality). One important
use for the information would be to assess the effect of folic acid
supplementation and fortification on NTD rates as well as rates of other
congenital malformations
7
Summary
Background
This Special Report 2009 reviews progress in developing and implementing public
health policies to raise periconceptional folate status in European countries up to the
end of 2007. Data on the prevalence of neural tube defects from 20 countries was
analysed to determine the extent to which neural tube defects had been prevented.
Our findings were disappointing and prompted us to make a number of
recommendations including fortifying a staple food with folic acid. This
recommendation is already under consideration by many governments.
Methods
The EUROCAT network has currently 43 population-based congenital anomaly
registries in 20 European countries collaborating in the epidemiological surveillance
of congenital anomalies. NTD cases (including livebirths, stillbirths and terminations
of pregnancy following prenatal diagnosis) were extracted from the EUROCAT
Central Registry database for 1980-2007 and prevalence rates were calculated. In
addition, representatives from 21 countries participating in or interested in joining
EUROCAT provided information about policy, health education campaigns and
surveys of folic acid supplement uptake in their country.
Results
By January 2005, 15 of the 20 countries contributing data to this report had
introduced an official policy advising women to take periconceptional
folic acid supplementation. Four countries (Austria, Belgium, Croatia, Germany) have
no official government policy at the time of writing, although professional groups
within them advise supplementation.
Half the countries have launched some type of health education campaign so that the
information about the protective effect of folic acid can reach women directly rather
than uniquely through health professionals
We found that the majority of women surveyed are still not taking folic acid
supplements periconceptionally. Only in the Netherlands and Denmark is the
periconceptional use of folic acid above 30%, the other countries not reaching 10%.
Mandatory fortification of a staple food (usually flour) with folic acid has been
8
seriously considered in eight countries contributing to this report (Denmark,
Germany, Ireland, Northern Netherlands, Norway, Poland, Switzerland, and the UK).
As of November 2009 food fortification with folic acid had not been implemented in
any European country although it is now widespread in North and South America and
in several countries in the Middle East.
Despite all measures taken to date, the majority of women in all countries surveyed
are not taking folic acid supplements prior to and for the first weeks after conception.
This study shows a declining trend for anencephaly in the years 1992-2007, but not
for spina bifida. We focused on this time period because all the folic acid advice and
campaigns started after 1992.
A significant decline in prevalence of NTD since1992 was found in Ireland, but not in
the UK. In Continental Europe (excluding Southern Europe), in spite of the significant
decrease in NTD prevalence in Northern Netherlands, the decrease for all registries
combined is slight and non-significant. In South Europe the decline in NTD
prevalence since 1992 was significant.
While livebirth NTD prevalence has decreased considerably in countries without a
folic acid supplementation policy due to the increase in prenatal diagnosis and
subsequent termination of affected pregnancies, the total prevalence has not
significantly decreased. Reduction of livebirth prevalence is still relying more on
prenatal screening and termination than on primary prevention with folic acid
supplementation. In order to distinguish between decreases in prevalence due to
primary prevention and those due to prenatal screening, information on terminations
of pregnancy is essential.
The existence of an expanded network of congenital anomaly registries in Europe,
collecting data on affected livebirths, stillbirths and terminations of pregnancy, is vital
to track progress towards the prevention of NTDs. Information on NTD prevalence
should be supplemented where possible by surveys of uptake of periconceptional
folic acid supplementation in the population, and by monitoring of serum levels of
folic acid.
9
Conclusion
The potential for preventing NTDs by periconceptional folic acid supplementation is
still far from being fulfilled in Europe. In order to achieve a reduction in NTD
prevalence, new efforts are needed in all countries to implement a combined strategy
to increase folate status by dietary means, increase uptake of folic acid supplements
periconceptionally, and to increase availability and identification of fortified foods
Mandatory fortification could improve folate status of all women of childbearing age,
substantially reduce NTD prevalence, and reduce socio-economic inequalities in
NTD prevalence. Additional benefits such as reduced specific cancer occurrence and
cognitive decline have also been reported, although these have not been supported
by randomised controlled trials.
As countries change their policies and practices regarding prevention of NTD,
continued monitoring of NTD prevalence is vitally important. This requires data from
population based registers of congenital anomalies with high ascertainment of cases
among livebirths, stillbirths and termination of pregnancy for fetal anomaly
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Part I
Overview of Neural Tube Defects
11
1. Introduction Across Europe, an estimated 4,500 pregnancies are affected by Neural Tube
Defects (NTD) each year. Evidence of a possible association between folic
acid and NTD has been described in the scientific literature for more than
three decades (Scott, Weir, & Kirke 1995). Since the early 1980s a number of
intervention trials examining the effects of periconceptional folic acid on the
prevalence of NTD have been published, with the first unambiguous evidence
of the effectiveness of periconceptional folic acid coming in 1991 on the
publication of the results of the Medical Research Council (MRC 1991). On the
basis of this trial, it has been estimated that improving folate status sufficiently
would result in the prevention of 72% of all NTD.
This report is an updated version of the EUROCAT NTD Report by the same
name published in 2005 and focuses on periconceptional folic acid policies
and implementation strategies across Europe since 1991 and the reported
prevalence rates of NTD until 2007. Contributions from EUROCAT (European
Surveillance of Congenital Anomalies) members representing 21 countries (20
countries with new data) are included in the form of chapters describing policy
and practice in their respective countries in relation to: periconceptional folic
acid supplementation, dietary advice, food fortification and women’s
knowledge about the advice and compliance with recommendations. These
are set within the context of laws relating to termination of pregnancy for fetal
abnormality and of what is known about the proportion of pregnancies that are
planned. The prevalence of NTD up to the end of 2007 is examined in relation
to policies on folic acid supplementation across Europe. Furthermore, since
2005 a variable on folic acid intake has been added to the set of data all
registries are sending to the Central registry. This report will show, for the first
time, the periconceptional folic acid intake among women giving birth to
malformed infants in several registries. The report will focus on NTD, as it is
for this group of anomalies that the body of evidence for the protective effect
of folic acid is strongest.
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2. The Public Health Response to Evidence Concerning the Protective Effect of Folic Acid
2.1 Periconceptional Folic Acid Policies in European Countries
Table 1 summarises periconceptional folic acid supplementation policies
around Europe. For more detail, the reader is advised to look at individual
country chapters in Part II of this Report.
By January 2005, 15 of the 20 countries contributing data to this report had
introduced an official policy advising women to take periconceptional folic acid
supplementation. The first governments to formulate such a policy were in the
Netherlands (1992), UK (1992) and Ireland (1993). Portugal recommends that
health workers should educate women about the benefits of folic acid; Malta
recommend raising folate status by dietary means only and four countries
(Austria, Belgium, Croatia, Germany) have no official government policy at the
time of writing, although professional groups within them advise
supplementation.
The recommendation for periconceptional folic acid supplements in most
countries is for a daily dose of 0.4 to 0.5 mg (except in Poland, where it is 1.0
mg, and Portugal, where no dose is specified). Higher doses, of 4 or 5 mg
daily, are usually recommended for women who have had a previous
pregnancy affected by an NTD. Some countries also have special
recommendations for women on anticonvulsant therapy.
Half the countries have launched some type of health education campaign
(Table1) so that the information about the protective effect of folic acid can
reach women directly rather than uniquely through health professionals. This
is particularly important as folic acid supplementation must start before
conception and therefore before the consultation of health professionals
during pregnancy. The details of these campaigns can be found in Part 2.
There is little evidence as to how often health education campaigns need to be
repeated for a sustained effect.
13
2.2 Uptake of Recommendations to Take Periconceptional Folic Acid Supplements Surveys of the use of folic acid supplements periconceptionally in European
countries are summarised in Table 1. Details are given in the individual
country chapters in Part 2 of this report. Details of the methodology of each
survey, where available, are given in Part 2, and figures shown in Table 1
should be interpreted in the light of these details.
Table 1: Current1 Folic Acid Supplementation Policy in European Countries
Country Periconceptional Folic Acid Policy 2
Status Year
current policy
introduced
Health education campaign
Year of study
% Women Using Folic Acid
Austria Unofficial 1998 No
1998 24% some part of advised period 10% for entire advised period
Belgium Unofficial - Being prepared
2006 48% some part of advised period 24% for entire advised period
Croatia Unofficial - Unofficial
2003 69% some part of advised period 20% for entire advised period
Denmark Official 1997 1999 and 2001
2000-2 22% of women who planned pregnancies took supplements at correct time
Finland Official 2004 Unofficial
2000 19% took FA before or in early pregnancy
France Official 2000 2000 and
2004
? 30% some part of advised period 10% for entire advised period
Germany Unofficial 1994 No
2000 4.3% for entire advised period
Hungary Official 1996 Ongoing 2006 69% of pregnant women Ireland Official 1993 1993 and
2000/2001 with Ulster
2002 23% periconceptionally
Italy Official 2004 2004 regional
2007 Depends very much on the region, range: 3-21%
Malta Dietary 1994 No 2000 74% some part of advised period 15% for entire advised period
Netherlands Official 1993 1995 2005 80% some part of advised period 51% for entire advised period
Norway Official 1998 1998 (website)
2000 46% periconceptionally
Poland Official 1997 Yes, but no date given
2005 70% some part of advised period 11% for entire advised period
Portugal Official 1998 No 2005 24% for entire advised period
14
Slovenia Official 1998 Unofficial 2007 88% some part of advised period 31% for entire advised period
Spain Official 2001 2002 2007 71% some part of advised period 17% for entire advised period
Sweden Official 1996 No 1997 8% some part of advised period
Switzerland Official 1996 2008 2003 98% some part of advised period 37% for entire advised period
UK Official 1992 1995 2002 45% periconceptionally Ukraine Official 2002 Unofficial
1 Policy as of December 2007
2 Recommended dose is as supplements unless otherwise stated
In all countries other than Netherlands, only a minority of women were found
to have taken folic acid supplements during the entire advised
periconceptional period. The highest uptake in the studies was recorded in
Netherlands, UK, Switzerland, Norway and Hungary with 30-51%
periconceptional uptake. Since these are the results of specific studies, we
added an extra variable to EDMP to assess folic acid intake for each woman.
In 2.3 the results are shown.
It should be noted that the countries in which the highest uptake rates were
found were those with official health education initiatives.
There is evidence that women of higher social status are more likely to know
of the benefits of taking supplemental folic acid and to be aware of the correct
timing (de Walle, van der Pal-de Bruin, & de Jong- van den Berg 1998;Sayers
et al. 1997;US Department of Health and Human Services 1993), potentially
leading to widening of socio-economic inequalities in NTD prevalence.
2.3 Monitoring of Intake of Folic Acid
Since 2005 EUROCAT has added an extra variable to the data entry
programme of EUROCAT in order to have more information on the
periconceptional intake of folic acid for individual cases. The results are shown
in the graph hereunder. In general over the years 2005-2007 the following
registries had some information on the use of folic acid periconceptionally:
Denmark (Odense), Italy (Tuscany and Emilia Romagna), Ireland (Dublin and
SE Ireland), Northern Netherlands, Switzerland (Vaud), Croatia (Zagreb), S
15
Portugal, Belgium (Antwerp), Spain (Basque country) and Germany (Saxony
Anhalt).
We restricted the figure (Figure 1) to include the 9 registries with information
on folic acid for more than 20% of their cases (periconceptional use, some use
or no use).
Figure 1: Use of folic acid, 2005-2007 (only for registries with 20% or more data on Folic Acid)
The figure shows that of the nine registries that have some information on
uptake, the uptake is very disappointing. The Northern Netherlands and
Odense (Denmark) have the highest percentage women taking folic acid in the
periconceptional period, 4 weeks before conception till 8 weeks after. Figure 2
shows the NTD prevalence rates shown for these 2 countries. This is the
prevalence excluding chromosomal anomalies because it is thought that folic
acid has the potential to be protective for multifactorial malformations, not for
chromosomal anomalies.
Use of folic acid, 2005-2007 (only for registries with 20% or more data on Folic Acid)
0
10
20
30
40
50
60
70
80
90
100
N Netherlands(NL)
Odense (DK) S Portugal (PT) Basque Country(ES)
EmiliaRomagna (IT)
Wales (GB) Saxony Anhalt(DE)
Zagreb (HR) Tuscany (IT)
perc
enta
ge
Periconceptional use Irregular use or starting >conception No use FA use unknown
16
Figure 2: Total Prevalence Neural Tube Defects (Excl Chromosomal) for Denmark (Odense) and Northern Netherlands, 1992-2007
There is a significant decreasing trend in the Netherlands ( χ2=5.1, p=0.02)
but not in Denmark ( χ2=0.52, p=0.47).
The 7 other registries reported less than 10% periconceptional use of folic
acid, so the overall uptake is very low. In 2005-2007 there were in total 41,516
cases with congenital malformations in the database. For 5,628 (13.6%) folic
acid information is known and the mothers of 969 (2.3%) cases took folic acid
in the periconceptional period. These numbers are too small to do a reliable
statistical analysis.
In the near future we will publish the results of a survey we did in all the
registries about the amount of information GPs, hospitals and midwives are
collecting routinely on folic acid intake before and during pregnancy.
2.4 Fortification of Food with Folic Acid
Mandatory fortification of a staple food (usually flour) with folic acid has been
seriously considered in eight countries contributing to this report (Denmark,
Germany, Ireland, Northern Netherlands, Norway, Poland, Switzerland, and
the UK) and the case for it is still being reviewed. As of November 2009 food
fortification with folic acid had not been implemented in any European country
Total Prevalence Neural Tube Defects (excl chromosomal) for Denmark (Odense) and Northern Netherlands, 1992-2007
0
2
4
6
8
10
12
14
16
18
20
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total Prevalence Odense (excl chromosomals) Total Prevalence NNL (excl chromosomals)
17
although it is now widespread in North and South America and in several
countries in the Middle East.
Food voluntarily fortified with folic acid (mainly breakfast cereals) is available
in many European countries. In a study investigating the effects of
consumption of folic acid-fortified bread compared with folic acid tablets, bread
was found to be equally effective in increasing folate status as indicated by
both increased red cell and serum folate concentrations(Armstrong NC. et al.
2001). However, it may be difficult for women to identify foods fortified with
folic acid and to determine the amount in relation to their needs due to
limitations/restrictions on food labelling.
3. NTD Prevalence Rates in Europe 1980-2007 NTD prevalence rates over time by country can be found in the Country
Specific Chapters of Part 2. Registry descriptions can be found on our new
website address: http://eurocat.bio-medical.co.uk. Most registries are
population-based and register affected fetuses / babies in livebirths, stillbirths
from 20 weeks gestation and terminations of pregnancy for fetal abnormality.
Laws in each country regarding whether and until what gestational age
termination of pregnancy for fetal abnormality is legal are summarised in Table
2.
Table 2: Laws Regulating Termination of Pregnancy for Fetal Abnormality
Country Is it Legal?
Gestational Age Limit for Non-Lethal Serious Anomalies
Gestational Age Limit for Lethal Anomalies
Austria Yes No upper limit No upper limit Belgium Yes No upper limit No upper limit Croatia Yes No upper limit No upper limit Denmark Yes Before viability No upper limit Finland Yes 24 weeks 24 weeks France Yes No upper limit No upper limit Germany Yes No upper limit No upper limit Hungary Yes No upper limit No upper limit Ireland No Not legal Not legal Italy Yes Before viability Before viability Malta No Not legal Not legal
18
Netherlands Yes 24 weeks No upper limit Norway Yes 18 weeks No upper limit Poland Yes <23 <23 Portugal Yes 24 weeks No upper limit Slowenia Yes No upper limit No upper limit Spain Yes 22 weeks 22 weeks Sweden Yes 22 weeks 22 weeks Switzerland Yes 24 weeks 24 weeks UK1 Yes No upper limit No upper limit Ukraine Yes 22 weeks 22 weeks
Information as of April 2008 1 Except Northern Ireland
3.1 Methods Data for all cases of NTD were extracted from the EUROCAT Central Registry
database 1980-2007.
Total prevalence rates were calculated as the number of affected livebirths,
stillbirths and terminations of pregnancy following prenatal diagnosis divided
by the total number of births (live and still) in the registry population. Livebirth
prevalence rates were calculated as the number of affected livebirths divided
by the total number of livebirths in the registry population.
Prevalence rates are given for anencephalus, spina bifida and all NTD
combined. Cases with both anencephalus and spina bifida were classified as
having anencephalus.
The χ2 for trend was used to test if prevalence was significantly decreasing or
increasing in time. Logistic regression was used in which the year of birth was
taken as independent variable for decreasing or increasing prevalence. The
test was done only for the total prevalence and total prevalence without chromosomal anomalies whenever appropriate. We did not test livebirth
prevalence as the influence of prenatal testing and termination of pregnancy is
becoming more important every year. Livebirth prevalence is not a reliable
measure for discussing the role of folic acid prevention.
Further details of methods can be found in the original EUROCAT special
report (2003) on the Prevention of Neural Tube Defects by Periconceptional
19
Folic Acid Supplementation in Europe on this website:
http://www.eurocat.ulster.ac.uk/pubdata/Folic-Acid.html.
3.2 Results Figure 3 shows a significantly decreasing prevalence of NTD from 1980 and
onwards. In the beginning of the nineties it became clear from the MRC study
(1991) and Czeizel’s Hungarian study (Czeizel 1993) that folic acid had a
preventive effect on NTDs. That was the impetus for launching campaigns in
several European countries. An effect of folic acid is therefore to be expected
from 1992 onwards and not before. As the main focus in this report is the
effect of periconceptional folic acid we tested the prevalence for significance
from 1992 onwards.
Figure 3: All Registries: Total (In- and Exclusive Chromosomal Anomalies) and Livebirth Prevalence Rates for Neural Tube Defects
The total prevalence for NTDs for all registries included in this report is
significantly decreasing from 1992 onwards. Over the years 1992-2007 χ2 for
trend =10.9, p=0.001. For the non-chromosomal NTDs χ2 for trend =9.3,
All registries: Total (in- and exclusive chromosomal anomalies) and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
16
18
20
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Total prevalence excl chromosomals Live birth prevalence
1991: year of the publication of the MRC trial
20
p=0.002. The figures below show whether this is due to spina bifida,
anencephaly or both.
Figure 4: All Registries: Total (In- and Exclusive Chromosomal Anomalies) and Livebirth Prevalence Rates for Spina Bifida
In figure 4 for the years 1992-2007 the χ2 for trend =1.1, p=0.29, the odds
ratio (OR) for year of birth is 0.997 (95% CI:.991-1.003), therefore no
significant decrease in trend for spina bifida over the years 1992-2007. For the
non-chromosomal spina bifida χ2 for trend =.31, p=0.58.
All registries: Total (in- and exclusive chromosomal anomalies) and Livebirth Prevalence Rates for Spina bifida
0
1
2
3
4
5
6
7
8
9
10
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Total prevalence excl chromosomals Live birth prevalence
21
Figure 5: All Registries: Total (In- and Exclusive Chromosomal anomalies) and Livebirth Prevalence Rates for Anencephaly
Figure 5 shows a significantly (slightly) decreasing trend for anencephaly over
the years 1992-2007, χ2 for trend =6.4, p=0.012, the odds ratio (OR) for year
of birth is 0.991 (95% CI:.984-.998). For the non-chromosomal anencephaly
χ2 for trend =6.9, p=0.009. This decrease might be real but can also be
caused by the fact that anencephaly is diagnosed earlier in pregnancy in
recent years and therefore less notified to the registries.
Figure 6 shows the total NTD prevalence for all countries in three time
periods.
All registries: Total (in- and exclusive chromosomal anomalies) and Livebirth Prevalence Rates for Anencephaly
0
1
2
3
4
5
6
7
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alenc
e per
10,00
0 birt
hs
Total prevalence Total prevalence excl chromosomals Live birth prevalence
22
Figure 6: Total Prevalence Rates for Neural Tube Defects, Per Country
The decrease in prevalence is most significant in Ireland. In May 2006, The
Food Safety Authority of Ireland (FSAI) and the Irish Department of Health &
Children (DoHC) recommended fortification of all bread (with the exception of
minor bread products) on a mandatory basis with folic acid at a level which
provides 120 µg per 100g of bread as consumed. It is mentioned earlier that
no EU country has mandatory food fortification with folic acid. However, this
was not implemented, and in 2008, the FSAI recommended postponement of
fortification, following preparatory studies by the implementation group which
showed that the rate of NTD affected births had decreased further. In addition,
there had also been a significant increase in folic acid intake in the Irish diet as
a result of increased voluntary fortification by food producers in recent years.
Furthermore, although termination of pregnancy is forbidden in Ireland, there
is always the possibility of terminations abroad.
Another country worth mentioning is the UK. The UK, together with Ireland
was the country with historical high rates for NTDs. In the recent period of
2005-2007 the prevalence is now of the same order as France, Belgium,
Malta, Denmark, Austria and Norway.
Total prevalence rates for Neural Tube Defects, per country
0
5
10
15
20
25
Irelan
d UKIta
ly
France
Belgium
Vaud (C
H)
Zagre
b (CR)
Malta
Northern
Neth
erlan
ds (N
L)
S Portugal
(PT)
Odense
(DK)
Spain
German
y
Styria
(AT)
Norway
Poland
Hungary
Finland
Ukraine
Country
Prev
alen
ce r
ate
per
10.0
00 b
irth
s
1980-2000 2001-2004 2005-2007
23
The chapter on France in the second part of this report shows that it is
especially the registry of Isle de la Reunion that has high prevalences over the
years 2002 -2007. This registry is one of the overseas departments of France
and is the outermost region of the European Union. It is located in the Indian
Ocean, east of Madagascar. The population is different genetically and
environmentally from Europe, so there is no reason to expect the prevalence
to be similar to that of other French registries.
NTD prevalence has changed over time, so regions with a high prevalence in
the past do not necessarily continue to have .a high prevalence. Figure 7
shows how the prevalences are changing in different parts of Europe.
Figure 7: Total Prevalence for Neural Tube Defects for Several Regions in Europe
Countries belonging to ‘South Europe” are: Italy, Croatia, Portugal, Malta and
Spain. “Continental Europe” is represented by France, Belgium, Switzerland,
Northern Netherlands, Denmark, Germany, Austria, Norway, Poland, Hungary,
Ukraine and Finland. Regions or countries that show a statistically declining
trend after 1992 are Ireland (p<.001) and Southern Europe (p<.001).
Total prevalence for Neural Tube Defects for several regions in Europe
0
5
10
15
20
25
30
35
40
45
50
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Ireland Total prevalence UK Total prevalence South Europe Total prevalence Continental Europe except South
24
In the beginning of this report we showed in which countries public health
campaigns about folic acid have taken place (Table 1). Figure 8 compares the
NTD prevalence for countries that have had a campaign to encourage folic
acid use with those that have not had a campaign. The countries that had a
campaign (between 1992-2007) are: Ireland, UK, France, the Netherlands,
Denmark, Spain, Norway, Poland and Hungary. There was no significant
decline in prevalence in either group. This was tested for the whole period of
1992-2007. However, it is clear from the picture that the lines come together in
recent years and that especially in countries with a public health campaign the
decline from 2003 onwards is obvious. For example in 2007 there is a
significant decline of 20% (OR=.80, 95% CI: .68-.95) in countries with a public
health campaign. We also commented before (figure3) that the total
prevalence for NTDs for all registries is significantly decreasing from 1992
onwards.
Figure 8: Total NTD Prevalence in Countries with and without a Public Health Campaign
Total NTD prevalence in countries with and without a public health campaign
0
1
2
3
4
5
6
7
8
9
10
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
birth years
Tota
l pre
vale
nce
per
10.0
00 b
irth
s
Total prevalence countries with a campaign Total prevalence countries without a campaign
25
3.3 Discussion This study shows a declining trend for NTDs in the years 1992-2007, driven by
the decline in anencephaly. We focused on this time period because all the
folic acid advice and campaigns started after 1992.
In Ireland it is difficult to distinguish the effect of the folic acid supplementation
policy on NTD prevalence rates from the decline in prevalence starting well
before the implementation of national policy. It is possible that one explanation
for this decline may be the increasing folate content of the Irish diet starting
before the national policy. However, since 1992 the decline has continued,
probably because of voluntarily fortified foods and better use of folic acid
supplementation.
In the UK registries participating in this study there has been no decline since
1992.
In Continental Europe (excluding Southern Europe), in spite of the significant
decrease in NTD prevalence rates in Northern Netherlands, the decrease for
all registries combined is slight and non-significant.
In South Europe the decline in prevalence since 1992 was significant. The
explanation for this could be increased consumption of folate rich / fortified
food and /or use of periconceptional folic acid supplementation, but it is also
known that increased socio-economic status decreases the risk for NTD.
While live birth NTD prevalence has decreased considerably in countries
without a folic acid supplementation policy due to the increase in prenatal
diagnosis and termination of affected pregnancies in these countries, the total
prevalence has not significantly decreased. This emphasizes two points.
Firstly, reduction of livebirth prevalence is still relying more on prenatal
screening and termination than on primary prevention with folic acid
supplementation. Secondly, in order to distinguish between decreases in
prevalence due to primary prevention and those due to prenatal screening,
information on terminations of pregnancy is essential.
26
The existence of an expanded network of congenital anomaly registries in
Europe, collecting data on affected livebirths, stillbirths and terminations of
pregnancy, is vital to track progress towards the prevention of NTDs.
Information on NTD prevalence should be supplemented where possible by
surveys of uptake of periconceptional folic acid supplementation in the
population, and by monitoring of serum levels of folic acid.
This study showed that registries have only little or no information about
whether the mother actually took folic acid periconceptionally. This is
disappointing. Apparently the perceived need for monitoring this is low.
Specific studies on this topic in contributing countries showed that only a
minority of women took supplements during the entire advised period.
Overall in Europe, some progress has been made in the primary prevention of
NTDs. This is especially true for anencephaly and for specific countries like
the Netherlands and Ireland. Southern Europe decreased significantly while
continental Europe only had a minor decrease in NTD prevalence. It is very
difficult to estimate how many affected pregnancies in Europe are being
prevented by use of folic acid. There is still room for improvement, especially
since the percentage of unplanned pregnancies is still high. Therefore, folic
acid fortification of staple foods might be an option to achieve significant
prevention of NTDs.
Mandatory fortification with folic acid has been introduced in around 50
countries worldwide as a strategy to help women increase their folate levels.
Reports from the US and Canada have shown an effective and significant
decline in NTDs (De Wals et al. 2007;Godwin et al. 2008;Williams et al. 2005).
Heseker et al. reported that countries with mandatory folic acid fortification
achieved a significant decrease in the prevalence of NTD. He concludes in his
study that the degree of reduction in NTD prevalence in a population is related
to the baseline NTD prevalence. This decline was independent of the amount
of folic acid administered and reveals a „floor effect‟ for folic acid preventable
NTDs. Thus, not all cases of NTDs are preventable by increasing folate intake
(Heseker et al. 2009). At the moment, mandatory fortification of folic acid is not
27
implemented in Europe. Fortification of staple foods with folic acid would
provide a more effective means of ensuring an adequate intake, especially for
those groups of women who are unlikely to plan their pregnancies or to
receive or respond to health promotion messages. Fortification together with
supplementation is likely to be a more cost-effective option than
supplementation only for preventing NTD, since a supplementation only policy
requires a health education campaign more extensive and effective and
possibly more frequent than those implemented so far.
In Europe there has been reluctance to proceed to mandatory food fortification
which we believe stems from two factors:
1) Lack of recognition of the public health importance of neural tube
defects, possibly because the great majority of NTD pregnancies
are now terminated, rendering them invisible to all but the family
affected.
2) The possibility of health risks related to raising the population folic
acid status. (Cornel, de Smit, & den Berg 2005)
There has been concern regarding the potential risk of masking the symptoms
of pernicious anaemia caused by vitamin B12 deficiency. If undiagnosed, there
is potential for irreversible neurological damage in those at high risk of this
deficiency, namely the elderly. However, it is argued that B12 deficiency can be
diagnosed simply with or without the presence of anaemia (Bower & Wald
1995). Furthermore, the masking of pernicious anaemia, which has
concerned people at a theoretical level, has not been observed in countries
with mandatory fortification of flour with folic acid.
Evidence continues to mount about the beneficial effects of folic acid for the
prevention of other congenital anomalies. The evidence regarding effects of
folic acid on cancer is not conclusive. Although there is evidence that folic acid
may be protective against the development of new cancers, there is concern
at the possibility that it may promote the development of undiagnosed pre-
malignant and malignant lesions. The European Food Safety Authority
summary report wrote: “There are currently insufficient data to allow a full
28
quantitative risk assessment of folic acid and cancer or to determine whether
there is a dose-response relationship or a threshold level of folic acid intake
associated with potential colorectal cancer risk. The evidence regarding the
effects of folic acid on cardiovascular disease is also inconclusive.
Observational studies suggested that high intakes of folic acid were
associated with a lower risk of CVD but randomised trials have not confirmed
these findings (ESCO 2009).
4. Conclusions
• The evidence that most NTD are preventable by increasing folate status
before conception is very strong
• Government response to this evidence has been variable in Europe.
Some countries have been slow to introduce policies while others very
actively promote periconceptional folic acid supplementation
• The majority of women in countries surveyed are still not taking folic acid
supplements periconceptionally
• Most countries have implemented some type of health education campaign
designed to reach women before conception. However, there are still five
countries that have had no campaigns at all. No difference was found in
the decrease in NTD prevalence between countries with and without a
campaign
• There is a decreasing trend of anencephaly over the years 1992-2007
which is significant but falls short of expectations; the prevalence of spina
bifida is not declining
• There is an immense challenge facing those involved in public health and
the care of prospective mothers to replace termination of pregnancy with
primary prevention by folic acid as the chief method of reducing the
number of infants affected by this very serious group of congenital
anomalies
• In order to achieve a reduction in NTD prevalence, new efforts are needed
in all countries to implement a combined strategy to:
- increase folate status by dietary means
- increase uptake of folic acid supplements periconceptionally
- increase availability and identifiability of fortified foods
29
• The possibility of preventing the majority of NTD through mandatory
fortification of a staple food has not yet been introduced by any of the
countries surveyed. Mandatory fortification could improve folate status of
all women of childbearing age, substantially reduce NTD prevalence, and
reduce socio-economic inequalities in NTD prevalence. Suggestions for
additional benefits such as reduced specific cancer occurrence and
cognitive decline are also made. However, evidence for this is not
supported by randomised controlled trials
• As countries change their policies and practices regarding prevention of
NTD, continued monitoring of NTD prevalence is vitally important. This
requires data from population based registers of congenital anomalies with
high ascertainment of cases among livebirths, stillbirths and termination of
pregnancy for fetal anomaly
30
5. References
Armstrong NC., Pentieva K., McPartlin, J., & Strain JJ "Comparison of the homocysteine-lowering effect of folic acid-fortified bread versus folic acid tablets.", Homocysteine Metabolism 3rd International Conference, Naples, p. 162.
Bower, C. & Wald, N. J. 1995, "Vitamin B12 deficiency and the fortification of food
with folic acid", Eur.J.Clin.Nutr., vol. 49, no. 11, pp. 787-793. Cornel, M. C., de Smit, D. J., & den Berg, L. T. W. D. 2005, "Folic acid - the scientific
debate as a base for public health policy", Reproductive Toxicology, vol. 20, no. 3, pp. 411-415.
Czeizel, A. E. 1993, "Prevention of congenital abnormalities by periconceptional
multivitamin supplementation", BMJ, vol. 306, no. 6893, pp. 1645-1648. de Walle, H. E. K., van der Pal-de Bruin, K. M., & de Jong- van den Berg, L. T. W.
Knowledge and use of folic acid in the Netherlands: are there socioeconomic differences? Teratology 57[35]. 1998.
De Wals, P., Tairou, F., Van Allen, M. I., Uh, S. H., Lowry, R. B., Sibbald, B., Evans,
J. A., Van den Hof, M. C., Zimmer, P., Crowley, M., Fernandez, B., Lee, N. S., & Niyonsenga, T. 2007, "Reduction in neural-tube defects after folic acid fortification in Canada", N.Engl.J.Med., vol. 357, no. 2, pp. 135-142.
ESCO. Folic acid: an update on scientific developments. ESCO Report on Analysis
of Risks and Benefits of Fortification of Food with Folic Acid. 1-22. 2009. Uppsala, Sweden.
Godwin, K. A., Sibbald, B., Bedard, T., Kuzeljevic, B., Lowry, R. B., & Arbour, L. 2008, "Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry", Can.J.Public Health, vol. 99, no. 4, pp. 271-275.
Heseker, H. B., Mason, J. B., Selhub, J., Rosenberg, I. H., & Jacques, P. F. 2009,
"Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid", Br.J.Nutr., vol. 102, no. 2, pp. 173-180.
MRC 1991, "Prevention of neural tube defects: results of the Medical Research
Council Vitamin Study. MRC Vitamin Study Research Group", Lancet, vol. 338, no. 8760, pp. 131-137.
Sayers, G. M., Hughes, N., Scallan, E., & Johnson, Z. 1997, "A survey of knowledge
and use of folic acid among women of child-bearing age in Dublin", J.Public Health Med., vol. 19, no. 3, pp. 328-332.
Scott, J. M., Weir, D. G., & Kirke, P. N. Folate and Neural Tube Defects. 329-360.
1995. New York, Marcel Dekker Inc, ed Lynn B. Bailey. Folate in Health and Disease.
US Department of Health and Human Services, F. a. D. A. Food standards: Amendment of the standards of identity for enriched grain products to require
31
addition of folic acid. 53305-53312. 1993. 58.
Williams, L. J., Rasmussen, S. A., Flores, A., Kirby, R. S., & Edmonds, L. D. 2005, "Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995-2002", Pediatrics, vol. 116, no. 3, pp. 580-586.
32
Report on Periconceptional Folic Acid Supplementation for Austria Prof Andrea Berghold, Prof Martin Haeusler
Folic Acid Supplementation Policy Austria has no official government recommendation for periconceptional folic acid
supplementation. But in 1988 the Austrian Pediatric Society and the Austrian Society
for Prenatal and Perinatal Medicine recommended periconceptional folic acid
supplementation (0.4 mg per day) for all women wishing to become pregnant.
Women who were already pregnant should start folic acid supplementation during
the first four weeks of gestation and continue until the 8th week. For women with a
high risk for recurrence of a neural tube defect, periconceptional folic acid
supplementation with 4 mg per day was recommended.
Food Fortification Policy Austria has no official food fortification policy but, as in many other countries, food
companies voluntarily fortify some breakfast cereals, malted drinks and some other
foods.
The Austrian government is discussing a proposal for mandated folic acid fortification
of flour. This may be decided in 2008. Problems to be solved beforehand include the
permission of the European Union and technical requirements of flour mills.
Health Education Initiatives Austria has undertaken no official health education initiatives on the role of folic
acid in reducing the risk for neural tube defects. No such initiatives are planned for
the near future in.
Knowledge and Uptake of Folic Acid A study carried out in St Pölten2 looked at maternal knowledge and periconceptional
folic acid supplementation among women delivered between 1.12.1997 and
31.3.1998. Women were interviewed with a standardized questionnaire. 238 women
participatedin the study and 234 questionnaires were analysed. 57 (24%) women
used folic acid; however 33 out of 57 did not start use until after 12 weeks´ gestation.
33
61 out of 161 (38%) who answered this question knew that folic acid prevented fetal
neural tube defects.
Proportion of Pregnancies that are Planned The proportion of pregnancies that are planned in Austria is unknown.
Laws Regarding Termination of Pregnancy (TOP) “Termination of pregnancy is allowed irrespective of gestational age, if the
pregnancy poses a serious threat to the pregnant woman’s physical or mental
health, or if there is a serious possibility that the child will be mentally or
physically handicapped”. However, in practice this is handled with caution to avoid
the accusation of euthanasia. In the case of non-lethal malformations, MFM
(maternal-fetal medicine) specialists in Austria agree to terminate pregnancies
before viability (i.e. < 24 weeks gestational age). In rare cases of severe
malformations diagnosed late they might agree to terminate pregnancies after
viability after consulting an ethics committee. In the case of lethal malformations
TOP is possible whenever the mother wishes. No medical doctor can be forced to
perform TOP.
References 1. Pollak A, Gruber W, Birnbacher R, Zwiauer K (1998) “Richtlinien zur
Praevention von Neuralrohredefekten durch perikonzeptionelle
Folsaeuresubstitution” Gynaekologisch-geburtshilfliche Rundschau Vol. 38 (1)
pp 55-56.
2. Zwiauer K, Groll D, Weissensteiner M (2000) “Folsaeuresubstitution bei
Schwangeren: Ergebnisse einer regionalen Untersuchung im Raum St.
Poelten”Paediatrie/Paedologie, Vol 6, pp 14-17.
34
Austria (Styria): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
16
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Austria (Styria): Total and Livebirth Prevalence Rates for Spina Bifida
0
1
2
3
4
5
6
7
8
9
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
35
Austria (Styria): Total and Livebirth Prevalence Rates for Anencephaly
0
0,5
1
1,5
2
2,5
3
3,5
4
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
36
Report on Periconceptional Folic Acid Supplementation for Belgium Prof Yves Gillerot, Andre Baguette and Vera Nelen
Folic Acid Supplementation Policy
In Belgium there is no official recommendation for periconceptional folic acid
supplementation. However, the unofficial policy is for all women planning a
pregnancy to take 0.4 mg folic acid daily and for women at high risk of having a
pregnancy affected by a neural tube defect to take 4 mg of folic acid daily. This
should be taken 2 or 3 weeks before conception and during the first 3 months of
pregnancy.
Food Fortification Policy There is no official folic acid food fortification policy in Belgium. However, fortified
products such as breakfast cereals are available for consumption.
Health Education Initiatives In 2005, the ONE (Office de la naissance et de l’enfance (Office of Birth and
Childhood)) in association with the ASBBF (Association Spina Bifida Belge
Francophone), ran a health education campaign which included leaflets, a website,
and information on radio and television. Letters about the benefits of
periconceptional folic acid were sent to family physicians and gynaecologists in the
French speaking area of Belgium. Information on why and when to take
periconceptional folic acid is also on the website of the Flemish counterpart of ONE
“Kind en Gezin (Child and family)”.
In 2009 a health education campaign, including leaflets and posters, started in the
province of Antwerp. The campaign was announced in the press and focused on
gynecologists, family doctors, pharmacies, midwives and child welfare.
Knowledge and Uptake of Folic Acid In 2006, a questionnaire regarding use of folic acid was administered to 195 breast
feeding women in the first week after delivery. 1 They had all delivered their first baby
and had been recruited for a study on pollutants in mothers’ milk. The results are in
Table 1.
37
Table 1 % of women using folic acid Flanders
N= 104 Wallonia N= 71
Brussels N= 20
Total N= 195
Before and during pregnancy 26 21 25 24
Only before pregnancy 13 6 0 9
Only during pregnancy 52 44 40 48
Total 90 70 65 81
Proportion of Pregnancies that are Planned No information provided
Laws Regarding Termination of Pregnancy Termination of pregnancy is legal up to the gestational age of 12 weeks. Beyond the
period of twelve weeks, the termination of pregnancy may be practised only when
the pursuit of the pregnancy severely endangers the health of the woman or when it
is certain that the unborn child will be affected by a disorder of a particular gravity,
recognized as incurable at the time of the diagnosis in which case there is no
gestational age limit.2
References
1. Personal communication from Vera Nelen 2. Translation of the "Code pénal" , Titre VII, art. 350 , 4°
38
Belgium (Hainaut and Antwerp): Total and Livebirth Prevalence Rates for Neural Tube Defects (2 registries together)
0
2
4
6
8
10
12
14
16
18
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Belgium (Hainaut and Antwerp): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
30
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Hainaut Total prevalence AntwerpLivebirth prevalence Hainaut Livebirth prevalence Antwerp
39
Belgium (Hainaut and Antwerp): Total and Livebirth Prevalence Rates for Spina Bifida (2 registries together)
0
2
4
6
8
10
12
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Belgium (Hainaut and Antwerp): Total and Livebirth Prevalence Rates for Spina Bifida
0
2
4
6
8
10
12
14
16
18
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Hainaut Total prevalence AntwerpLivebirth prevalence Hainaut Livebirth prevalence Antwerp
40
Belgium (Hainaut and Antwerp): Total and Livebirth Prevalence Rates for Anencephaly (2 registries together)
0
1
2
3
4
5
6
7
8
9
10
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Belgium (Hainaut and Antwerp): Total Prevalence Rates for Anencephaly
0
2
4
6
8
10
12
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Hainaut Total prevalence Antwerp
41
Report on Periconceptional Folic Acid Supplementation for Croatia Dr Visnja Tokic, Dr Ingeborg Barisic, Dr Romana Gjergja
Folic Acid Supplementation Policy
There is no official folic acid supplementation policy in Croatia and none is being
planned. Most gynaecologists and paediatricians in Croatia advise every woman to
take folic acid (0.4 mg per day) at least 4 weeks before starting a pregnancy until the
12th week of pregnancy. For women who have had a previous pregnancy affected
by a neural tube defect, the dosage is 4 mg per day for the above-mentioned period.
There are few folic acid supplementation products: FOLIC PLUS – (400 μg in 3
tablets) Natural Wealth, FOLIC ACID CAPS (800 μg) - Twinlab, PRENATAL tablets
(800 μg ) – Natural Wealth, PRE-NATAL caps (400 μg in 2 capsules), FOLACIN (5
mg) – Jadran Galenski Laboratorij. There is no funding for folic acid products during
pregnancy; pregnant women have to pay for it themselves.
Food Fortification Policy There is no mandatory food fortification in Croatia. Of course, one can get fortified
food from other European countries, and it is not prohibited to have and to sell it in
shops, but there are no statistics or studies on that issue.
Health Education Initiatives There is no official health education initiative in Croatia, but there are many
initiatives by the media (TV, Internet, journals, gynecologists and pediatricians,
especially private ones). An example is in the Maternity Unit “Sveti Duh” in the city of
Zagreb; there is a “Club of pregnant women” and they discuss their habits and
nutrition during the pregnancy. A major function of that Club is to educate women
about healthy nutrition, for instance, the importance of taking ample folic acid. The
Internet page is: www.klubtrudnica.net
There are some useful Croatian sites on the Internet:
• www.poliklinika-harni.hr
• www.mameibebe.net
• www.vasezdravlje.com
• www.iskon.hr/bebe
42
Knowledge and Uptake of Folic Acid The studies on dietary habits and folic acid supplementation in Croatia are limited;
there are a few studies relating to anaemia in children, congenital heart diseases,
neurological disease in children and arteriosclerosis. In 2003 we administered a
questionnaire to pregnant women in “Sveti Duh Hospital” in Zagreb (upublished
data): 495 pregnant women completed the questionnaire during their attendance at
the prenatal clinic. Median age was 30.8 years (± 3.7). 74% (368/495) of women
were aware of the role of folic acid in the prevention of birth defects. The sources of
the information were: the media (53%), health professionals (39%) and friends (9%).
64% of women were informed too late: 48% during the first pregnancy and 16% after
the first pregnancy. 71% of women (349/495) expressed the need for more
information on folic acid supplementation in pregnancy. 69% (343/495) of women
were taking folic acid, but only 20% of them (70/343) during the appropriate
periconceptional period. This was despite the fact that 75% (371/495) of the
pregnancies were planned. Most of the women (71%) could not specify the daily
dosage taken. As a group, women who were not taking folic acid were less educated
than women who were taking it. 20% of women not taking folic acid had graduated
from faculty or high school, while 41% of women who were taking it had graduated
from faculty or high school. (p<0.01). Parity, marital and economic status did not
influence folic acid intake. Out of 371 planned pregnancies, folic acid was taken
during the appropriate time period by only 19% of women (70/371), while 27%
(100/371) did not take folic acid supplementation at all.
In a more recent study (2006),1 Pucarin-Cvetkovic et al looked at 100 women of
childbearing-age (range 20-30 years), mean age 24±3.7. The subjects were
residents of Zagreb and its surroundings. The results based on the data obtained
through 24-h recall showed that the mean intake of naturally occurring food folate
and folic acid from fortified cereals was 156±72.2 μg/day. The mean value of the
serum folate was within the normal range: 7-28 nmol/L – no clinical deficit was
identified. Differences were found (p<0.001) between the subjects who consumed
folic acid supplements in drinks and tablets and subjects who did not. Differences
were also found between subjects who took folic acid supplements in drinks or
tablets and subjects who took folate only through foodstuffs, and did not consume
folic acid supplements (p=0.040).
43
Proportion of Pregnancies that are Planned In one small unpublished study, 75% of pregnancies were planned. No other
information is available.
Laws Regarding Termination of Pregnancy Termination of pregnancy for fetal abnormality is legal up to 24 weeks of gestation in
Croatia. After 24 weeks gestation it is not legal, but if a life-threatening anomaly is
found on ultrasound scan after 24 weeks, there is some possibility of termination of
pregnancy if it is approved by the Hospital Commission.
References 1. Pucarin-Cvetkovic J, Kaic-Rak A, Matanic D, Zah T, Petrovic Z, Car A, Degac
KA, Rak D. Dietary habits and folate status in women of childbearing age in
Croatia. Coll Atropol 2006;30(1):97-102.
Croatia (Zagreb): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
44
Croatia (Zagreb): Total and Livebirth Prevalence Rates for Spina Bifida
0
2
4
6
8
10
12
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Croatia (Zagreb): Total and Livebirth Prevalence Rates for Anencephaly
0
1
2
3
4
5
6
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
45
Report on Periconceptional Folic Acid Supplementation for Denmark Dr Marianne Christiansen
Folic Acid Supplementation Policy The official folic acid supplementation policy in Denmark was introduced in March
1997 by the Danish Veterinary and Food Administration. It is as follows: Women
planning a pregnancy are recommended to take a multivitamin tablet or a folic acid
tablet containing 400 µg of folic acid per day, or to take in 400 µg of folic acid per day
through diet, if possible. In the official recommendations, it is mentioned that for
practical reasons the recommendation is to take a folic acid supplementation of 400
µg per day since achieving 400 µg of folic acid through the diet would require a
change of diet for most women. The supplementation should begin when the
pregnancy is planned and continue until 3 months of gestation. Women with
increased risk of having a pregnancy with a neural tube defect due to malabsorption,
long-term use of certain medications, diabetes mellitus or neural tube defects in
relatives are recommended a folic acid supplement of 400 µg per day through
multivitamin / folic acid tablets. Available preparations include Folsyre” 0.4 mg folic
acid, “Gravitamin” containing 0.4mg folic acid amongst other vitamins, and “Gravid”
containing 0.4mg folic acid amongst other vitamins.
Women who have previously had a fetus with a neural tube defect, who themselves
have a neural tube defect or whose partner has a neural tube defect are
recommended to take 5 mg of folic acid per day. This supplementation is
recommended from when the pregnancy is planned and until 2 months of gestation.
The available supplementation is “Folimet” 5 mg folic acid.
The official policy was declared by the Danish Veterinary and Food Administration
after a working group had made a report on the issue.1 The official policy differs
slightly from the recommendations given in the report regarding the time period in
which pregnant women should take supplementation. The policy is also stated in the
Directives of Antenatal and Maternity Care given by the Danish National Board of
Health 1998.2
46
Food Fortification Policy In 2002 the Danish Veterinary and Food Administration established a working group
to re-evaluate the issue of folic acid fortification of food. In April 2003 this group
published a report recommending that the existing official recommendations
regarding supplementation should be followed and that mandatory folic acid
fortification of food should be introduced in Denmark. However, no action has been
taken yet and the official policy established in 1997 remains unchanged; there is no
mandatory folic acid fortification of food in Denmark.
Health Education Initiatives There is an official health education initiative in Denmark to inform women about the
role of folic acid in reducing the risk for neural tube defects: The Danish Veterinary
and Food Administration have had press releases with information about the policy;
the first was on March 3, 1997, another on June 11, 1999. Leaflets addressing
women planning pregnancy have been published by the Danish Veterinary and Food
Administration and distributed to general practitioners, specialists in gynaecology
and obstetrics, gynaecological / obstetrical departments of the Danish hospitals,
pharmacies and drugstores. The leaflets were first distributed in 1999 and again in
2001. In 2001 the number of leaflets distributed was 105,000 (the number of total
births in Denmark per year is approximately 65,000). Publications from the National
Board of Health addressing women planning a pregnancy and pregnant women also
contain information about the official folic acid recommendations. There have been
no paper or television advertisements, but the issue has been covered in some
newspaper articles, television programs about health issues and in magazines
concerning health, pregnancy and children. The Danish Veterinary and Food
Administration has started an ongoing campaign with flyers, go-cards and posters to
download from their website.
Knowledge and Uptake of Folic Acid In 2004, a paper called ”Low compliance with recommendations on folic acid use in
relation to pregnancy: is there a need for fortification?” (4) was published in Public
Health Nutrition. It was a cohort study on pregnant women in Denmark. 22,000
pregnant women were recruited for The Danish National Birth Cohort between
November 2000 and February 2002. Use of dietary supplements was recorded.
Compliance with the recommendation was related to the information campaign that
47
took place during the second half of 2001. An increase was seen in the proportion of
women complying with the recommendation in the study period and this coincided
with the information campaign events. However, even at the end of the period, only
22.3% of the women who had planned their pregnancy fully complied with the
recommendation. No increase at all was seen in periconceptional folic acid use
among women with unplanned pregnancies.
Regarding the dietary habits of women of child bearing age, the working group under
the Veterinary and Food Administration (1) have calculated the intake of folate in
Denmark using data from the Danish Dietary Survey performed in 1995. The results
were that women of child-bearing age in Denmark have a mean intake of 248 µg
folate per day through the diet; only 5% get 400 µg or more.
Proportion of Pregnancies which are Planned
No national study has been published from Denmark on the proportion of
pregnancies which are planned. In the Danish version of the report done by the
working group under the Danish Veterinary and Food Administration (1) it is
assumed that the number is a little higher than in the United States where
approximately half of the pregnancies are planned, since compliance with
contraception in Denmark is rather high. However a regional study in Denmark was
published in 2001.5 The study population (n=3516) was recruited among pregnant
women attending Odense University Hospital, Funen County (the region covered by
the EUROCAT register), in the period November 1994-January 1996. In this study
68% of the women with accepted pregnancies stated that the pregnancy was
planned. The representativity of this study sample was judged by comparing the age
distribution and the parity profile of the women in the study population with the
national figures. No pronounced difference was found, indicating that the study
sample can be considered a representative sub sample of the Danish population.
Laws Regarding Termination of Pregnancy Women in Denmark have the right to have a termination of pregnancy before 12
weeks of gestation. After 12 weeks a woman can have her pregnancy terminated
after obtaining permission from a special committee of two doctors and an employee
at the Social Centre (one committee in each County). If a severe congenital anomaly
48
is diagnosed, the upper gestational age for termination is usually 22 weeks.
Termination may be permitted later, but only if the congenital anomaly is so severe
that survival by birth would be impossible.
References
1. Rasmussen LB, Andersen NL, Andersson G, Lange AP, Rasmussen K, Skak-
Iversen L, Skovby F, Ovesen L (1998), “Folate and neural tube defects:
Recommendations from a Danish working group” Dan Med Bull, Vol 45, pp
213-217
2. The Danish National Board of Health: Directives of Antenatal and Maternity
Care (1998) 3. Olsen J, Melbye M, Olsen SF, Sorensen TI, Aaby P, Andersen AM, Taxbol D,
Hansen KD, Juhl M, Schow TB, Sorensen HT, Andresen J, Mortensen EL,
Olesen AW, Sondergaard C (2001), “The Danish National Birth Cohort – its
background, structure and aim” Scand J Public Health, Vol 29, No 4, pp 300-
307
4. Knudsen VK, Orozovo-Bekkevold I, Rasmussen LB, Mikkelsen TB,
Michaelsen FK, Olsen SF (2004), “Low Compliance with recommendations on
Folic Acid Use in relation to pregnancy: Is there a Need for Fortification?”,
Public Health Nutrition, Vol 7, No 7, pp 843-850.
5. Rasch V, Knudsen L B, Wielandt H (2001), “Pregnancy planning and
acceptance among Danish pregnant women” Acta Obstetricia et
Gynecologica Scandinavica, Vol 80, No 11, pp 1030-1035
49
Denmark (Odense): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Denmark (Odense): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
50
Denmark (Odense): Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
51
Report on Periconpceptional Folic Acid Supplementation for Finland Dr Annukka Ritvanen
Folic Acid Supplementation Policy In 1994 the Finnish Ministry of Social Affairs and Health set up an expert group to
prepare a National Recommendation on Periconceptional Use of Folic Acid. The
recommendations, issued in 1995, were sent to all medical professionals, health
care centres, hospitals and pharmaceutical companies.1 The recommendations
were also published in the leading Finnish scientific medical paper in 1996.2 The
recommendations were reviewed by an expert group of the Ministry of Social Affairs
and Health in 2004, and in the autumn of 2004 the new recommendations on folic
acid were published as part of a National Nutrition Recommendation for small
children and pregnant and breast feeding mothers. The main changes in the new
recommendations, compared with the old ones from 1995, are in the first section
concerning ordinary pregnancies. The 1995 recommendation was purely dietary,
while in the 2004 recommendation a supplement of a 0.4 mg folic acid tablet is
recommended for those with an unbalanced diet poor in folate content.
The present official recommendation on folic acid supplementation has three
sections:
1. Prevention of first occurrence of NTD in ordinary pregnancies
The recommendation is to take 0.4 mg folate daily in diet periconceptionally.
• A normal, balanced low-fat and low-sugar diet, with abundant fresh
vegetables, berries and fruit as well as wholemeal products, rich in
folate, is recommended for all women planning a pregnancy and in
early pregnancy, in order to obtain folate equivalent to at least 0.4 mg
folic acid daily.
• A daily supplement of a 0.4 mg folic acid tablet, to be used
periconceptionally, is recommended for all women planning a
pregnancy and in early pregnancy, whose diet does not contain
enough fresh vegetables, berries, fruit or wholemeal products.
• A daily supplement of a 0.4 mg folic acid tablet can also be taken
periconceptionally by women with balanced, folate-rich diet, if they
want to make sure they will obtain an adequate amount of folic acid.
52
2. Prevention of first occurrence of NTD in special situations
The recommendation is to take a daily supplement of a 0.4 mg folic acid tablet
periconceptionally.
• In addition to a balanced diet, a daily supplement of a 0.4 mg folic acid
tablet, to be used periconceptionally, is recommended for women who
are planning a pregnancy and who may, for various reasons, have
potential folate deficiency in early pregnancy.
• Potential folate deficiency may occur, if the mother has a very
unbalanced diet, treatment with antiepileptics (phenytoin and
barbiturates), long-term treatment with sulphonamides, celiac disease
or other severe intestinal malabsorption or heavy alcohol consumption.
• Folic acid supplementation may also be considered, if the mother has,
insulin dependent diabetes, clomiphene treatment, valproate or
carbamazepine treatment or neural tube defects among more distant
relatives.
3. Prevention of recurrence of NTD
The recommendation is to take a 4 mg folic acid tablet daily,
periconceptionally
• There is an increased risk (2–3%) of fetal NTD in the following
situations:
a) the parents have had a common child or fetus with NTD.
b) either parent has had a child or fetus with NTD with another partner
c) either the mother or the father has had NTD him/herself.
• The use of a 4 mg folic acid supplement as tablets should take place
under the control of a doctor, and this supplement is only available with
a doctor's prescription. Before starting this supplementation, or if
needed also during the supplementation, the maternal serum B12 level
should be checked in order to make sure that there is no deficiency of
vitamin B12. The reason for this is that an amount of 1mg folic acid can
conceal megaloblastic anaemia, associated with deficiency of vitamin
B12, and thus prevent the detection of deficiency of this vitamin.
• Folic acid supplementation does not give complete protection against
fetal NTD, so in pregnancies in high risk families, prenatal screening
53
and diagnosis should be offered to women. Women who want prenatal
investigations should be referred to a prenatal diagnostic unit in a
university hospital early in pregnancy.
• The Social Insurance Institution does not reimburse preventive folic
acid supplementation.
• Folic acid supplementation is started, when contraception is stopped or
at the latest, at the beginning of the menstrual period after which a
pregnancy is hoped for, and the supplementation will be continued until
the end of the 12th week of pregnancy (i.e. starting 4 weeks before
conception and continuing until the end of the 12th week of
pregnancy).
The expert group of STM still considered that the balanced diet, according to the
National Nutrition Recommendation, usually guarantees an adequate supply of
folate, and that routine folic acid supplementation is not needed. It has, however,
been observed that the average intake of folate by Finnish women (224 μg) is less
than the Finnish Nutrition Recommendation (400 μg for pregnant women and those
planning a pregnancy and 300 μg for other women). The expert group considered
that a minimum of 5 to 6 portions of vegetables, berries and fruit should be eaten
daily. If the mother eats very few fresh vegetables, berries and fruit, she should be
advised to increase her intake of them in order to improve the balance of her diet
and to ensure intake of the recommended amount of folate.3
The expert group also reported that the easiest way to implement supplementation of
0.4 mg folic acid is to use a multivitamin preparation with an adequate amount of
folic acid. There are a few preparations in the Finnish market which, taken according
to instructions, give a daily supply of 0.4 mg folic acid. Preparations with lower
concentrations of folic acid are not recommended for use, as by increasing the
dosage, the supply of other nutrients becomes too high.
A recommendation on folic acid supplementation published by the National
Research and Development Centre for Welfare and Health STAKES in 1999 was
approximately the same as the present recommendation.4
54
Food Fortification Policy Fortification of food products with folic acid was not considered justifiable in Finland
(STM 1995). Fortification of food products with folic acid has been monitored by the
Finnish Food Safety Authority (previously National Food Agency) with the support of
the Ministry of Social Affairs and Health and under the direction of a broad-based
group of experts. The report of the expert group, published in December 2001, did
not recommend fortification of basic food products with folic acid.5
Health Education Initiatives There has been no health education initiative on folic acid supplementation in
Finland, but information is being given at schools and by the maternity clinics and
child welfare clinics. The issue has been widely presented in women’s magazines.
Folic Acid Knowledge and Uptake A study was carried out in the year 2000 in 114 public maternity clinics around
Finland. Public Health nurses or midwives completed a questionnaire with the
women during their first visit to the maternity clinic. 547 women participated in the
study; 6 % of the women refused. The women had their first antenatal visit on
average during the ninth gestational week. 65 % of respondents had heard about
folic acid; young and less educated women had heard of it less often than others.
The women had received information on the effect of folic acid on pregnancy and
fetuses from newspapers and magazines, public maternity clinics and health care
centres, and from schools and other educational institutions. Drug advertisements
and friends were a more common source of information than were doctors and
pharmacists. 10 % of women knew about the effects of folic acid on pregnancy and
the fetus. 29 % of women could list at least one food product containing folic acid. 45
% of women had used at least one preparation containing vitamins and / or trace
elements before and / or in early pregnancy. 34 % of women had consumed a folic
acid supplement (19% of them before pregnancy and /or in early pregnancy).6
Proportion of Pregnancies which are Planned 547 women were interviewed by a midwife / nurse during their first prenatal care visit
at approximately 9 weeks gestation. Data were collected over a one month period in
114 maternity centres in Finland in the year 2000. 6 % of the women refused to
participate. Between 37 % and 86 % of the pregnancies were planned, depending on
55
the interpretation of the concept of “planned”. 60 % of the women changed their life
style in early pregnancy. However, 75 % of these changes were made only after the
woman found out about her pregnancy.7
What women thought about getting pregnant prior to the pregnancy, by age of
mother (%) <25 25-29 30-34 >35 All
I wished to get pregnant as soon as possible 33 39 41 32 37I thought the pregnancy may begin by its own time 48 53 47 45 49I wished to get pregnant later 9 4 2 5 5I did not want to get pregnant 4 1 3 3 2I didn't think about it 3 3 4 9 4Getting pregnant or the time was not important 4 1 3 6 3
According to a recent study in Northern Finland the percentage of wanted
pregnancies seems to be high even among primiparous mothers.8
Laws Regarding Termination of Pregnancy Termination of pregnancy is allowed up to 12 weeks gestation (12+0 gw) for many
indications by permission of one or two doctors and up to 20 weeks (20+0 gw) by
special permission of the National Supervisory Authority for Welfare and Health
(Valvira). If the mother’s life is in danger, the pregnancy can be terminated at any
gestational age. Termination for severe fetal abnormality can be done up to 24
weeks only by special permission of the National Supervisory Authority for Welfare
and Health (Valvira).
References 1. Sosiaali- ja terveysministerion asiantuntijaryhma (1995). Hoitosuositus.
Foolihappo ja hermostoputken sulkeutumishäiriöt. 33/623/95
2. STM asiantuntijaryhmä (1996). Hoitosuositus. Foolihappo ja hermostoputken
sulkeutumishäiriöt. Duodecim Vol 112, p 963.
3. Hasunen K, Kalavainen M, Keinonen H, Lagström H, Lyytikäinen A, Nurttila A,
Peltola T, Talvia S (2004). The Child, Family and Food. Nutrition
recommendations for infants and young children as well as pregnant and
breastfeeding mothers. Helsinki 2004. Publications of the Ministry of Social
Affairs and Health 2004:11
4. Stakes (1999) Seulontatutkimukset ja yhteistyö äitiyshuollossa. Suositukset
Oppaita 34. Viisainen K (toim). Helsinki 1999
56
5. National Food Agency together with Ministry of Social Affairs and Health
(2001). Elintarvikevirasto. Elintarvikkeiden täydentäminen foolihapolla -
mallinnettu saanti suomalaisilla aikuisilla. Elintarvikeviraston julkaisuja Vol 11,
Helsinki
6. Ritvanen A, Sihvo S, Gissler M. Knowledge about folic acid among pregnant
women in Finland. 7th European Symposium on the Prevention of Congenital
Anomalies. Heidelberg May 29-June 1, 2003 (presentation) published in
Reproductive Toxicology vol 18, number 1 (January-February 2004).
7. Sihvo S, Ritvanen A, Hemminki E. Pregnancy planning and lifestyle changes.
7th International Congress of Behavioural Medicine 28-31 Aug, 2002 Helsinki.
International Journal of Behavioural Medicine 2002:9 (suppl. 1): 249-50.
8. Pouta A, Järvelin MR, Hemminki E, Sovio U, Hartikainen AL. Mothers and
daughters: intergenerational patterns of reproduction. Eur J Public Health.
2005 Apr;15 (2):
Finland: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
57
Finland: Total and Livebirth Prevalence Rate for Spina Bifida
0
2
4
6
8
10
12
14
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Finland: Total and Livebirth Prevalence Rates for Anencephaly
0
2
4
6
8
10
12
14
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
58
Report on Periconceptional Folic Acid Supplementation for France Dr Janine Goujard and Elisabeth Robert-Gnansia
Policy on Folic Acid Supplementation In 1995, the French Pediatric Society published a recommendation to pregnant
women to take a daily dose of 0.2 mg daily of folic acid supplements. They also
advised women of child-bearing age to increase folate intake through diet.
A second awareness was raised in 1997 by the National College of Obstetrics and
Gynecology. They advised the same folic acid supplementation level of 0.2 mg daily
during the periconceptional period, reinforcing the position of the French Pediatric
Society. The folic acid status of the French women was considered to be good.
However, encouragement was given for a multi-vitamin therapy at a daily dose of
400 µg of folic acid in high-risk situations (teenagers, discontinuation of oral
contraception, alcoholic women, women of low social economic class).
In 1999, the State Secretary of Health set up an expert group to prepare national
recommendations which were issued in August 2000. The advice for most women
planning a pregnancy was a daily dose of 0.4 mg of folic acid from 4 weeks before
conception to 8 weeks after conception. In February 2003, two pharmaceutical
companies marketed the first tablets ever sold in France containing the exact dosage
of 0.4 mg of folic acid alone. The Ministry of health agreed to refund women for 65%
of the cost for these tablets when they are prescribed to prevent malformations.
For women with a previous NTD pregnancy and women taking antiepileptic
medication, the recommendation was 5 mg folic acid daily; this dosage has been
marketed for many years.
Food Fortification Policy There is no mandatory food fortification. However, some fortified breakfast cereals
are available (around 160-170 mg /100 g, more for “Cornflakes: 300 mg /100 g”) in
most supermarkets.
59
Health Education Initiatives
In 2000, recommendations for a diet rich in folate, calcium, iodine and iron were
made in an illustrated leaflet addressed to women of child-bearing age. In this
booklet, there is a small paragraph for women planning pregnancy, saying that folic
acid is needed to “prevent intra uterine growth retardation and various severe
malformations of the baby “.
In 2004, the French “Association Spina Bifida” edited an information leaflet on folic
acid, to be distributed all over the country and placed in waiting rooms of physicians,
family planning centres, pharmacies, etc.
The pharmaceutical companies marketing 0.4 mg folic acid tablets have organized
conferences and training programmes for gynaecologists across the country in order
to stimulate prescription of folic acid by physicians.
Advice about periconceptional folic acid has been spread via TV and newspapers.
Knowledge and Uptake of Folic Acid
Two studies using the same protocol were done in public and private obstetric units
in Paris in 1995 and 1999. The 1999 study (2) carried out on 735 women interviewed
2 or 3 days after the delivery showed that 55.1 % (405/735) had heard of folic acid
but most often with no knowledge of its effect. 24.3% (177/728) reported the use of
one of the products containing folic acid (with or without additional multivitamins or
minerals) present on a list with the pictures of the boxes. But only 1.0% (8/735) took
the folic acid in the recommended period. Even these results were better than those
of the 1995 survey (1) in which only 0.5 % - 3/733- took folic acid during the
recommended period. Clearly, the messages from the “non official”
recommendations issued in the country in 1995 and 1997 were not heard.
In a recent study in Brittany, more than 200 women were surveyed after delivery.
10% reported taking periconceptional folic acid correctly. A further 30% took it
during pregnancy only. (personal communication Dr. Hubert Journel)
60
Proportion of pregnancies which are planned
No information is available. Laws Regarding Termination of Pregnancy
There is no upper gestational age limit on termination of pregnancy for fetal
abnormality with approval by experts if “there is a high probability that the fetus is
affected by a particularly severe condition with no effective therapy available at the
time of prenatal diagnosis” (law of July 1994).
References 1. De Vigan C, Raoult B, Vodovar V, Goujard J (1996), “Prévention de
l’anencéphalie et du spina bifida par l’acide folique : situation en région
parisienne. (Folic acid prevention of anencephalus and spina bifida : statusin
Paris area)” BEH, Vol 15, pp 69-71
2. Dehé S, Vodovar V, Vérité V, Goujard J (2000), “Prevention primaire des
anomalies de fermeture du tube neural par supplementation
periconceptionnelle en acide folique. Situation à Paris en 1999 (Primary
prevention of neural tube defects by supplementation in folic acid. 1999 status
in Paris)” BEH, Vol 21, pp 87-9
3. Dr Hubert Journel, (Cordinator of Groupe Folate France)
personal communication
Additional Reading: Three chapters in books addressed to the French medical
establishment have been written
4. Goujard J (1995), “Acide Folique et prévention des anomalies de fermeture du
tube neural”, In: “Les traitements médicamenteux du fetus”, Eds: Pons G,
Cabrol D et Tournaire M, Springer-Verlag, pp 229-236
5. Goujard J, Vodovar V, De Vigan C (1996), “Prévention et dépistage des
anomalies de fermeture du tube neural”, 25éme Journées Nationales de la
Société Française de Médecine Périnatale Eds: Treisser A, Puech F, Arnette
Blackwell, Paris, pp 277-286
6. Goujard J (In Press), “Prevention des anomalies de fermeture du tube neural :
supplémentation periconceptionnelle en acide folique”, In: “Les medicaments
en Périnatologie”, Eds: Pons G , Cabrol D, Moriette G, Masson, Paris
61
France (Strasbourg, Paris, Central East France, Isle de Reunion): Total and Livebirth Prevalence Rates for Neural Tube Defects (all 4 registries together)
0
2
4
6
8
10
12
14
16
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
0
5
10
15
20
25
1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Paris Total prevalence StrasbourgLivebirth prevalence Paris Livebirth prevalence Strasbourg
62
France (Central East France, Isle de Reunion): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
16
18
20
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Central East France Total prevalence Isle de ReunionLivebirth prevalence Central East France Livebirth prevalence Isle de Reunion
France (Strasbourg, Paris, Central East France, Isle de Reunion): Total and Livebirth Prevalence Rates for Spina Bifida (all 4 registries together)
0
1
2
3
4
5
6
7
8
9
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
63
France (Strasbourg, Paris): Total and Livebirth Prevalence Rates for Spina bifida
0
2
4
6
8
10
12
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Strasbourg Total prevalence ParisLivebirth prevalence Strasbourg Livebirth prevalence Paris
France (Central East France, Isle de Reunion): Total and Livebirth Prevalence Rates for Spina Bifida
0
2
4
6
8
10
12
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
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er 1
0,00
0 bi
rths
Total prevalence Central East France Total prevalence Isle de ReunionLivebirth prevalence Central East France Livebirth prevalence Isle de Reunion
64
France (Strasbourg, Paris, Central East France, Isle de Reunion): Total and Livebirth Prevalence Rates for Anencephaly (all 4 registries together)
0
1
2
3
4
5
6
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
France (Strasbourg, Paris, Central East France, Isle de Reunion): Total Prevalence Rates for Anencephaly
0
1
2
3
4
5
6
7
8
9
10
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
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er 1
0,00
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rths
Strasbourg (FR) Paris (FR) Central East France Isle de Reunion (FR)
65
Report on Periconceptional Folic Acid Supplementation for Germany Dr Simone Pötzsch, Prof Volker Steinbicker (emeritus)
Folic Acid Supplementation Policy While many bodies have made recommendations regarding folic acid intake for
women planning a pregnancy, there are no official governmental guidelines on this
point in Germany.
In 1994/95 recommendations published by the German Nutrition Society, the
German Society of Obstetrics and Gynaecology, the German Society of Human
Genetics, the German Society of Paediatrics and Adolescent Medicine, and the
German Society of Neuropaediatrics advised 0.4 mg folic acid daily for women
planning a pregnancy, and 4 mg of folic acid daily for women with a previous
pregnancy affected with a neural tube defect (NTD). The recommendations specified
a period starting four weeks prior to pregnancy and lasting till the end of the first
trimester (Koletzko 1994, Koletzko 1995).
In 2000 the Societies of Nutrition in Germany (DGE), Austria (ÖGE) and Switzerland
(SVE, SGE) published the “Reference Values for Nutrient Intake” for the German
speaking countries (Deutsche Gesellschaft für Ernährung 2000). The reference
values for folic acid intake can be found in table 1.
Table 1: Reference values for folic acid intake (Deutsche Gesellschaft für Ernährung
2000)
Age groups Folic acid (μg equivalent daily)
Infants
0 – 4 months 60
4 – 12 months 80
Children
1 – 4 years 200
4 – under 7 years 300
7 – under 10 years 300
10 – under 13 years 400
13 – under 15 years 400
66
Adolescents and adults
15 – under 19 years 400
19 – under 25 years 400
15 – under 65 years 400
51 – under 65 years 400
65 years and elder 400
Pregnant women 600
Breastfeeding women 600
Food Fortification Policy In 2006 the German Society for Nutrition (DGE) published a position paper
containing strategies to improve folic acid supplementation in Germany. Therein the
DGE argues for the supplementation of flour with 0.15 mg folic acid/ 100 g flour to
achieve an additional intake of 0.135 mg/d for men and 0.106 mg/d for women
(Deutsche Gesellschaft für Ernährung 2006).
In Germany folic acid is classified as a supplementary food, and hence does not fall
under drug approval requirements. The Nutritive Value Declaration Regulation
(Nährwertkennzeichnungsverordnung) (Thamm 1999) claims that 100 g of flour
should be fortified with up to 15 per cent of the recommended daily dose of 0.2 mg of
folic acid. However, the maximum daily intake must not exceed three times the
recommended daily dose (i.e. 0.6 mg folic acid).
In Germany no authorisation is required for the fortification of foods for general
consumption with folic acid. As many manufacturers have used this option in recent
years, there is now a wide range of foods enriched with folic acid brought on the
market (Bundesinstitut für Risikoforschung 2005).
A major problem in marketing food enriched with folic acid is the fact that in Germany
it is not allowed to refer to potentially beneficial effects on health for advertisement
purposes, e.g. "... contributes to the prevention of NTD". (Law on Food and Articles
of Consumption - Lebensmittel- und Bedarfsgegenstandsgesetz) (Thamm 1999).
67
Among the medical societies in Germany, only the Society of Paediatrics and
Adolescent Medicine has published a recommendation for flour enriched with folate
(Koletzko 2000). Some foodstuffs, such as bread, cereal grains and fruit juice, are
fortified with folic acid. However, there is still no official list in Germany.
On 8 May 2000, a meeting of experts took place in Berlin where the necessity of
improving the measures for preventing NTD was discussed. Participants in the
meeting included physicians, representatives of malformation registries, politicians,
representatives of the food industry, consumer federations, scientists,
pharmaceutical companies, and others. However, this meeting failed to establish a
common position regarding the fortification of food with folic acid. Instead, the
participants decided to form a working group to this end.
In autumn 2003 the “Folic Acid and Health Working Group” (www.ak-folsaeure.de)
was formed in which representatives of professional medical societies, scientific
institutions, the food industry, parents’ initiatives and the Swiss Federal Commission
for Nutrition work together. The German Federal Ministry for Health and the Federal
Ministry of Consumer Protection, Food and Agriculture send their observers to
meetings of this group. The work focuses on introducing folic acid fortification of
basic food in Germany. As a first step, a consensus paper was published in the
German medical journal "Deutsches Ärzteblatt" in 2004 (Koletzko 2004). The
consensus paper is highly appreciated among German physicians.
In 2005, the Federal Institute for Risk Assessment (Bundesinstitut für
Risikobewertung - BfR) published a final report referring to the provision of folic acid
for the German population. Because of gaps in the knowledge about the risk
assessment, the authors recommended that folic acid supplementation for women of
childbearing age should be 0.4 mg/d. Furthermore the BfR postulated additional
information campaigns in the population and highlighted the point that the
effectiveness of supplementation of wheat or salt with folic acid has not been proven
yet (Bundesinstitut für Risikobewertung 2005).
Health Education Initiatives There has been no official health education initiative. Departments of the Federal
Ministry of Health, Federal Ministry of Consumer Protection, Food and Agriculture,
68
and the German Nutrition Society are aiming to improve health knowledge and raise
awareness of the population. Although they all have analysed the effects of folic acid
intake, a concerted action for improving knowledge in this field has not been
launched to date.
Knowledge and Uptake of Folic Acid in Women
• In 2000 a study in Munich was performed by Egen, comprising two inquiries: (i)
during the first inquiry 346 women were interviewed after delivery in 1996, (ii) the
second inquiry interviewing 402 women was performed in 1998.
• Between 1996 and 1998 an information campaign had taken place. The study
results revealed a periconceptional folic acid intake of 400 μg per day in seven
women (2%) in 1996, whereas this number was 20 (5%) in 1998 (Egen 1999).
• In the Federal State of Saxony-Anhalt an inquiry was made in maternity hospitals
in 1998. A total of 567 women were interviewed after childbirth about whether
they had taken folic acid prior to or after confirmed conception. Only 34 women
(6%) reported to have taken folic acid prior to conception. A second inquiry was
conducted in 2000, comprising a total of 1,224 women after delivery. The total
number of women who had taken folic acid prior to conception amounted to only
53 (4.3%) (Heinz 2001).
Knowledge about Vitamins and the Nutritional Behaviour of Students An inquiry about the nutritional behaviour and knowledge about vitamins among
4,332 students aged 16-21 in the Federal State of Saxony-Anhalt revealed that only
4.5% of those interviewed were aware that folic acid is a vitamin and only 0.7% of
the students knew the function of folic acid in the organism. Boys and girls did not
differ in their knowledge. In contrast, more than 95% of those interviewed knew that
alcohol, nicotine and X-rays should be avoided during pregnancy, information, which
is taught in school lessons. This suggests that information about folic acid and
pregnancy should also be given at school (Seelig 2005; Pötzsch et al. 2006).
Knowledge and Practice of Health Care Professionals in Recommending a Supplementary Folic Acid Intake From October 1997 to March 1999 the first German Health Survey was carried out
(German National Health Interview and Examination Survey)
(Bundesgesundheitssurvey 1999, Mensink 1998). One point of this study was
69
"Subjective Statements on the Daily Intake of Drugs from Selected Drug Groups".
For women between 18 and 45 years of age the following ranking of drug use was
established: (i) in the western federal states 30% oral contraceptives, 11.5% thyroid
drugs, 8.1% vitamins; (ii) in the eastern federal states 47% oral contraceptives, 10%
thyroid drugs, 5.5% vitamins (Knopf 1999).
Gynaecologists
• In 1998 the Malformation Monitoring System Saxony-Anhalt performed an
anonymous inquiry among 234 gynaecologists regarding pre- and post
conceptional administration of folic acid. The questionnaire was returned by 104
gynaecologists (44.4%). 76.9% of them said they would supply folic acid after
confirmation of conception, whereas 87.5% would recommend preconceptional
intake.
• In 1996 a total of 27 gynaecologists in Munich were interviewed about their
attitude towards prophylactic folic acid supplementation. Nine gynaecologists
(38%) recommended taking folic acid preconceptionally, two (8%) recommended
taking folic acid at the beginning of pregnancy, four (17%) recommended taking
folic acid only in cases within a family history of NTD, whereas nine (37%) did not
give any recommendation at all.
• Following an intervention campaign in 1998, 20 (74%) gynaecologists
recommended taking preconceptional folic acid, four (15%) recommended taking
folic acid with the beginning of pregnancy and three (11%) only in case of a
family history of NTD (N = 27) (Egen 2000).
Pharmacists
• In 1996 Egen interviewed 21 pharmacists in Munich about their
recommendations for prophylactic folic acid. Eight pharmacists (38%)
recommended taking folic acid in the beginning of pregnancy, whereas five (24%)
did not give any recommendation, and eight pharmacists (38%) recommended a
periconceptional intake (Egen 2000).
• In 2000, Malformation Monitoring Saxony-Anhalt conducted an anonymous
inquiry among 598 pharmacists with regard to prophylactic folic acid. Only 104
(17.4%) of the interviewed pharmacists returned the questionnaire, of which 82
(79%) recommended both a pre- and post-conceptional folic acid intake. Twelve
pharmacists (11.5%) recommended taking folic acid preconceptionally, and eight
70
(7.7%) recommended it only in the post-conceptional phase. Two pharmacists
(1.8%) did not give any recommendation at all (Kästner 2001).
Nutritional Habits and Other Supplementary Vitamins A large part of the population in Germany does not reach the recommended folate
intake.
• The German Nutrition Report 2004 stated that the daily intake of folic acid among
women aged 19 to 24 years was 198 μg/d in the western and 184 μg/d in the
eastern federal states. The average daily intake of 215 μg/d among all women is
still below the reference value of 400 μg/d (Deutsche Gesellschaft für Ernährung
2004).
• In the German National Health Interview and Examination Survey
(Bundesgesundheitssurvey 1999, Mensink 1998) a total of 1,266 women
between 18 and 40 years of age were interviewed. The average daily folic acid
intake was 119 μg free folic acid equivalents. In 80.6% of all women the daily
intake of folic acid was less than 150 μg. 8.1% of the women in the western
federal states (N = 1,231) and 5.5% of the women in the eastern federal states (N
= 601) between 18 and 45 years of age were taking multivitamin tablets and 0.6%
of them were taking folic acid tablets (Heinz 2001).
• The Bavarian Food Consumer Study (Bayerische Verzehrstudie 1995) found out
that the average daily folic acid intake for women was 0.08 mg folic acid
equivalents (Bayerisches Staatsministerium für Ernährung, Landwirtschaft und
Forsten1997).
Women’s Sources of Information about Folic Acid The German National Health Interview and Examination Survey (N = 562)
(Bundesgesundheitssurvey 1999, Mensink 1999) found out that women received
their information about folic acid from the following sources:
• 29.3% physicians
• 28.1% journals
• 14.8% TV
• 9.1% friends
• 8.5% newspaper
• 7.1% health insurance
• 3.1% radio
71
Egen (1999) interviewed 35 women and found they received their information from
the following sources:
• 77% gynecologists
• 14% self-information
• 6% professionals
• 3% genetic counselling
Investigations in Saxony-Anhalt (2000) (Heinz 2001) found out that women received
their information from the following sources (table 2):
Table 2: Women’s sources of information about folic acid in Saxony-Anhalt (Heinz
2001)
Sources of information
Prior to pregnancy During pregnancy
N = 227 Rate in per
cent
N = 1,057 Rate in per
cent
Physicians 137 60.4 784 74.2
Radio/ TV/
magazines
44 19.4 51 4.8
Books 33 14.5 61 5.7
Friends 30 13.2 47 4.4
Others 17 7.5 28 2.7
Partner 13 5.7 28 2.6
Relatives 13 5.7 25 2.4
Pharmacists 11 4.8 27 2.6
Information
centre
0 0 6 0.6
Proportion of Pregnancies which are planned
• Egen conducted a study comprising 131 women right after delivery, of which 94
(72%) confirmed that they had planned their pregnancy. In 1998 Egen again
interviewed 118 women after delivery. 80 (68%) out of them had planned their
pregnancy (Egen 1999).
72
• In 1998 a study was performed in Saxony-Anhalt, comprising 567 women after
delivery who were asked whether or not their pregnancy had been intended. A
total of 391 (69%) of the women confirmed that their pregnancy had been
planned. Again, in 2000 a study was conducted in Saxony-Anhalt in the course of
which 1,224 newly delivered women were interviewed. 806 (66%) answered that
their pregnancy had been planned.
• Declaration of the final report of the Federal Institute for Risk Assessment
(Bundesinstitut für Risikobewertung) referring to the supply of the German
population with folic acid: 40-50% unplanned pregnancies are estimated (no
source known).
Molecular-Genetic Investigations Within the German National Health Interview and Examination Survey
(Bundesgesundheitssurvey 1999) 994 women were checked for the presence of a
C677T mutation. 421 women (42.4%) did not carry this mutation. 455 women
(45.7%) were heterozygous and 118 (11.9%) were homozygous for the C677T
mutation. These women exhibited a significantly higher homocysteine level (Thamm
M – personal information).
Laws Regarding Termination of Pregnancy In Germany, termination of pregnancy is allowed irrespective of gestational age, if
the pregnancy implies a serious threat to the pregnant woman’s physical or mental
health, or if the fetus is affected by malformations.
73
References 1. Bayerisches Staatsministerium für Ernährung, Landwirtschaft und Forsten
(1997): Ernährungssituation in Bayern. Stand und Entwicklung.
Abschlussbericht zum Forschungsbericht Bayerische Verzehrsstudie (BVS).
veröffentlicht unter: www.stmelf.bayern.de.
2. Bundesgesundheitssurvey 1998 (1999): Gesundheitswesen (2) Sonderheft:
55- 222.
3. Bundesinstitut für Risikobewertung (BfR)/ Federal institute for risk
assessement (2005): Folic acid intake of the German population – Final report
on the research project (Folsäureversorgung der deutschen Bevölkerung.
Abschlussbericht zum Forschungsvorhaben). BfR-Hausdruckerei Dahlem.
ISBSN 3-9381163-16-X
4. Koletzko B, von Kries R. (1994): Prävention von Neuralrohrdefekten durch
Folsäurezufuhr in der Frühschwangerschaft. Der Frauenarzt Vol 35, 1007- 10.
5. Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für
Ernährung, Schweizerische Gesellschaft für Ernährungsforschung,
Schweizerische Gesellschaft für Ernährung (D-A-CH) (2000): Referenzwerte
für die Nährstoffzufuhr. Umschau Braus-Verlag Frankfurt/ Main.
6. Deutsche Gesellschaft für Ernährung (DGE) (2006): Strategien zur
Verbesserung der Folatversorgung in Deutschland. Nutzen und Risiken.
Positionspapier der Deutschen Gesellschaft für Ernährung.
7. Deutsche Gesellschaft für Ernährung (DGE) (2004): Ernährungsbericht 2004.
Bonn.
8. Deutsche Gesellschaft für Ernährung (DGE) (2000): Ernährungsbericht 2000.
Bonn.
9. Egen V (2000): Die Bedeutung des Gynäkologen für die Umsetzung der
Folsäureprophylaxe von Neuralrohrdefekten. Geburtshilfe Frauenheilkunde Vol
60, 183.
10. Egen V (1999): Die Prophylaxe von Neuralrohrdefekten durch Folsäure:
Umsetzung eines medizinischen Forschungsergebnisses in der Praxis.
Dissertation an der Medizinischen Fakultät der Ludwig-Maximilians- Universität
München.
11. Egen V, Hasford J (2000): Folic acid- and Iodide- Prophylaxis in Pregnancy -
Results from the PEGASUS-Project. Pharmacoepidemiology and Drug Safety
Vol 9, 1-150.
74
12. Koletzko B, von Kries R. (1995): Prävention von Neuralrohrdefekten durch
Folsäurezufuhr in der Frühschwangerschaft. Gynäkologische und
Geburtshilfliche Rundschau Vol 35, 2-5.
13. Heinz J. (2001): Fehlbildungsprävention durch Folsäure – Kenntnisstand und
geübte Einnahmepraxis von Frauen in Sachsen-Anhalt. Diplom-Arbeit
Hochschule Anhalt (FH) Abteilung Bernburg.
14. Kästner S, Rösch C. et al (2001): Empfehlungen zur perikonzeptionellen
Folsäureeinnahme – werden Apotheker ihrer Beraterfunktion gerecht.
Apothekerblatt Sachsen-Anhalt (5).
15. Knopf H et al (1999): Subjektive Angaben zur täglichen Anwendung
ausgewählter Arzneimittelgruppen - Erste Ergebnisse des
Bundesgesundheitssurveys 1998. Gesundheitswesen Vol 61, 151-157.
16. Koletzko B, von Kries R. (2000): Folatanreicherung von Getreideprodukten zur
Prävention angeborener Fehlbildungen und vaskulärer Erkrankungen.
Monatsschrift Kinderheilkunde Vol 3, 286.
17. Koletzko B, von Kries R. (1995): Prävention von Neuralrohrdefekten durch
Folsäurezufuhr in der Frühschwangerschaft. Der Kinderarzt Vol 26, 187-190.
18. Koletzko B et al. (2004): Gesundheitliche Bedeutung der Folsäurezufuhr. (AK
Folsäure und Gesundheit) Gesundheitswesen Vol 101 (23), 1670-1683.
19. Mensink G. B. M, Hermann-Kunz E et al. (1998): Der Ernährungssurvey.
Gesundheitswesen Vol 60, 83-86.
20. Mensink G. B. M, Stöbel A (1999). Einnahme von
Nahrungsergänzungspräparaten und Ernährungsverhalten.
Gesundheitswesen (61) Sonderheft Vol 2, 132-137.
21. Mensink G. B. M, Thamm M et al. (1999). Der Ernährungssurvey 1998 –
Methoden und erste Ergebnisse. Gesundheitswesen (61): 200-206 Rösch C,
Steinbicker V. (1999). Fehlbildungsprotektion durch Folsäure – Empfehlungen
und Realität. Gesundheitswesen Vol 61, 82-85.
22. Pötzsch S, Hoyer-Schuschke J, Seelig M, Steinbicker V (2006): Knowledge
among young people about folic acid and its importance during pregnancy : a
survey in the Federal State of Saxony-Anhalt (Germany). Journal of applied
genetics. - Poznan, ISSN 1234-1983, Bd. 47 (2006), 2, 187-190.
23. Seelig M (2005): "Einige Untersuchungen zum Ernährungsverhalten von
Schülerinnen und Schülern Sachsen-Anhalts unter besonderer
75
Berücksichtigung des Kenntnisstandes der Fehlbildungsprotektion durch
Folsäure", Diplomarbeit Hochschule-Anhalt (FH) Abteilung Bernburg.
24. Seelig M (2006): Kenntnisstand von SchülerInnen in Sachsen-Anhalt zum
Thema "Folsäure und Schwangerschaft" in Päd - Praktische Pädiatrie. -
Hamburg : OmniMed-Verl.-Ges., ISSN 0949-7641, Bd. 12 (2006), 3, 197-203.
25. Seelig M, Pötzsch S, Steinbicker V (2005): Folsäure - ein Vitamin mit
besonderer präventivmedizinischer Bedeutung, Ergebnisse einer
repräsentativen Schülerbefragung in Sachsen-Anhalt. In: Ernährungsumschau
52 (2005), 8: 315-319.
26. Thamm M, Mensink G. B. M, Thierfelder W (1999): Folsäureversorgung von
Frauen im gebärfähigen Alter. Gesundheitswesen Vol 61, 207-212.
Additional Summary on folic acid/metafoline for Germany Dr Annette Queißer-Luft and short explanation folic acid versus 5-Methyl-
Tetrahydrofolat (from Prof. Dr. K. Pietrzik, Rheinische Frierich-Wilhelms-Universität,
Bonn)
The intake of folate via normal foods and the folate status of (parts of) the European
population are below the reference values. At the same time, the incidence of neural
tube defects (NTD) in Europe is considered unacceptably high. Earlier studies have
shown a preventive effect of folic acid on the occurrence of NTDs. Therefore, to
increase the intake of folate/ folic acid is a major public health objective in Europe.
Up to now, women of childbearing age were advised to take supplements with a
minimum of 400 µg folic acid from four weeks before to two to three months after
conception However, only a small percentage of women follow this advice. Therefore, in
many European countries fortification of flour or another staple food with folic acid has been
considered an alternative strategy.
The daily peri-conceptionel intake of additional 400µg folic acid is recommended to
prevent NTDs. Various studies showed risk reductions between 35 to 70% for NTDs.
Multivitamins containing 800µg folic acid showed a close to 100% for NRD and a
significant decrease for congenital heart defects and defects of the urinary tract.
Concerning major birth defects prevention these products seem to be superior.
76
Taking into account the recent development (increasing use of folic acid i.e. by
fortifying food like cereal and fruit juices) long term overdoses, more than 1mg
tolerable upper intake level, have to be avoided due to the masking of
haematological symptoms of a vitamin B12 deficiency. For this purpose natural folate
[5-Methyl-Tetrahydrofolate (5-MTHF)] would be the best choice. At first a masking of
a B12- deficiency is highly unlikely and second it is the biological active form of the
vitamin in the human body. This is of main importance for people with an enzymatic
polymorphism of the folate metabolism, resulting in a lower 5-MTHFR production.
Approximately 10% of any population show a homozygote MTHFR 677C→T-
polymorphism, resulting in a 75% decrease of MTHFR activity. Thus the supply of
this “missing” substance would have the strongest impact in terms of a broad
prevention strategy. As homozygote constellations do have a higher risk for NTDs
and also the risk for heterozygote persons is slightly increased, a beneficial folate
supply through 5-MTHF intake could be the optimal result for 50% of the population.
Well respected studies on bioavailability and reduction of Homocysteine levels
proved 5-MTHF (Calcium L-Methylfolate) to be equivalent to folic acid. Long term
studies on the elevation of the Erythrocytic folate levels even resulted in a significant
superiority of the active form.
Germany (Saxony Anhalt and Mainz): Total and Livebirth Prevalence Rates for Neural Tube Defects (2 registries together)
0
5
10
15
20
25
30
35
19801981
19821983
19841985
19861987
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19941995
19961997
19981999
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Germany (Saxony Anhalt and Mainz): Total and Livebirth Prevalence Rates for Neural Tube Defects
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25
30
35
40
45
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19841985
19861987
19881989
19901991
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Germany (Saxony Anhalt and Mainz): Total and Livebirth Prevalence Rates for Spina Bifida (2 registries together)
0
5
10
15
20
25
30
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19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
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Germany (Saxony Anhalt and Mainz): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
30
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
20002001
20022003
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Germany (Saxony Anhalt and Mainz): Total and Livebirth Prevalence Rates for Anencephaly (2 registries together)
0
2
4
6
8
10
12
14
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
19981999
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20022003
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Germany (Saxony Anhalt and Mainz): Total Prevalence Rates for Anencephaly
0
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4
6
8
10
12
19801981
19821983
19841985
19861987
19881989
19901991
19921993
19941995
19961997
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0,00
0 bi
rths
Total prevalence Saxony Anhalt Total prevalence Mainz
80
Report on Periconceptional Folic Acid Supplementation for Hungary By Janos Sandor
Folic Acid Supplementation Policy In 1996, the National Institute for Health Promotion released a recommendation for
women planning a pregnancy. The recommendation was for women to take a
supplement of 0.4 mg/day folic acid during the preparation for pregnancy.
In 1998, The National Board of Hungarian Gynaecologists issued guidelines for
vitamin and mineral supplementation during pregnancy. They recommended 0.4
mg/day folic acid throughout pregnancy in order to prevent neural tube defects. 1
They did not mention preconceptional folic acid.
Food Fortification Policy There is no mandatory food fortification in Hungary, and the fortification of a staple
food is not planned in the near future. The authorization and production of fortified
foods is allowed and is under legal regulation, but there is no available database
about fortified foods at the moment. A wide variety of imported breakfast cereals are
available. In 1998 a special kind of bread fortified with folic acid became accessible
with very limited success. In the absence of supporting health education, the lack of
interest led to its disappearance it from the market.
Health Education Initiatives In Hungary, public health nurses support women preparing for pregnancy, during
pregnancy and after delivery. This service is provided free of charge and is financed
by municipalities. Since the early 1980s, these nurses have been required to direct
the attention of women to the fact that folic acid supplementation is effective in the
prevention of anaemia. More recently, they have begun to tell women about the
benefits of folic acid in helping to prevent congenital anomalies.
Knowledge and Uptake of Folic Acid The most recent investigations on folic acid intake are the following:
69% of Hungarian pregnant women regularly take products containing folic acid
(usually multivitamins). 93% of them start the intake after the 7th week of pregnancy.
81
(45.85% start in 1st trimester, 41.68% in 2nd trimester, and 12.46% in 3rd trimester)
The daily dose is under 0.5 mg for 85% of pregnant women.2
The Dietary survey in Hungary (2003-2004) investigated the nutritional habits of a
representative sample. A nested sample was investigated according to vitamin
intake as well. This sub-sample consisted of 587 women over 18.3
Daily folate intake (μg/day) in Hungary among women
Age group Mean SD N 18-34 132.3 47.5 176 35-59 132.3 47.5 176 60+ 124.6 42.9 235 18+ 131 46.9 587
Proportion of Pregnancies that are Planned
67.4% of pregnancies in Hungary were found to be planned in a study published in
2006. 4 The figures broken down by maternal age were as follows:
15-19 year: 48.3%
20-24 year: 54.2%
25-29 year: 62.5%
30-34 year: 67.1%
35-39 year: 67.4%
40-44 year: 66.1%
45-49 year: 64.6%
Laws Regarding Termination of Pregnancy Induced abortion is regulated by the 1992 Act Number LXXIX on the protection of
foetal life which modified the 1973 regulations. According to the 1992 act, a
pregnancy may be interrupted if it seriously endangers the health of the mother or
the foetus, if the pregnancy is the consequence of a crime or if the mother is in a
grave crisis situation. According to the definition of the Decree of the Ministry of
Health No 18/2000(June 29) a grave crisis situation occurs when it causes bodily or
mental impairment or socially intolerable situation.5
82
If the probability of a genetic or congenital impairment is above 50%,
then termination of pregnancy is allowed until a gestational age of 20 weeks. If the
diagnosis requires more time, then this period can be extended until 24 weeks.
Finally, if the intrauterine diagnosis is a disease or condition which is
incompatible with life, there is no gestational age limit on termination of pregnancy.
References 1. Szülészeti és Nőgyógyászati Szakmai Kollégium (National Board of
Hungarian Gynaecologists): Szakmai állásfoglalás a terhesség alatti vitamin
és ásványi anyag supplementatio kérdéséről (Guideline for vitamin and
mineral supplementation during pregnancy). Magyar Nőorvosok Lapja, 62(1):
63-65, 1999.
2. Bognar M, Hauser P et al: A magyarországi várandósok folsavszedési
szokásai (Unsuitable practice of folic acid supplementation in pregnant
women in Hungary). Orvosi Hetilap, 147(34): 1633-1638, 2006.
3. Rodler I, Bíró L et al: Táplálkozási vizsgálat Magyarországon, 2003-2004
(Dietary survey in Hungary), 2003-2004. Orvosi Hetilap, 146 (34): 1781-1789.
4. Kamarás Ferenc: Kívánt és nem kívánt terhességek, gyermekek (Wanted and
unwanted pregnancies, children). Demográfia, 49 (2-3): 150-172, 2006.
5. Központi Statisztikai Hivatal (Hungarian Central Statistical Office):
Demográfiai évkönyv 2005 (Demographic Yearbook 2005). KSH, Budapest,
2006. (ISSN 0237-7594)
83
Hungary: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Hungary: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
84
Hungary: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
85
Report on Folic Acid Supplementation for Republic of Ireland Dr Robert McDonnell
Folic Acid Supplementation Policy Recommendations were made by the Irish Department of Health and Children in
1993 that if there is any possibility of pregnancy, a woman should take an additional
400 µg of folic acid daily prior to conception and during the first twelve weeks of
pregnancy. The preferred means of supplementation is by a daily folic acid tablet.
The policy is promoted through the Department’s Health Promotion Unit by way of
leaflets and promotion campaigns.
Food Fortification Policy Voluntary fortification of foods (particularly cereal and milk) by food producers has
been in existence for a number of years, and it was expected that mandatory
fortification will be implemented in 2008 (see below).
In a 1998 report to the Minister for Health1, the Food Safety Advisory Board of
Ireland (an official body) recommended that food fortification should be considered
as a complimentary measure to supplementation (rather than an alternative).
In 2004, a report by the Nutrition Sub-committee of the Food Safety Authority of
Ireland (which has replaced the Food Safety Advisory Board) undertook a risk
benefit analysis of fortification in Ireland and concluded that folic acid fortification at
200µg /100g would have a significant effect in preventing NTD without resulting in an
appreciable risk of adverse health effects from high intakes in any population
subgroup. In 2005 the Department of Health and Children set up a national
committee to examine folic acid food fortification (www.folicacid.ie).
In May 2006, the Report of the National Committee on Folic Acid Food Fortification2
was launched by the Food Safety Authority of Ireland (FSAI) and the Irish
Department of Health & Children (DoHC). This made a number of recommendations,
the first of which was the fortification of all bread (with the exception of minor bread
products) on a mandatory basis with folic acid at a level which provides 120 µg per
100g of bread as consumed. The report and its recommendations were adopted as
government policy. Following this, the FSAI established a Folic Acid Implementation
86
Group in November 2006 to progress and implement the Report’s recommendations.
The report is available via link: http://www.fsai.ie/assets/0/86/204/ca0a6f81-e3a1-
4e7c-8284-bc363f8ed091.pdf
However, in 2008, the FSAI recommended postponement of fortification, following
preparatory studies by the implementation group which showed that the rate of NTD
affected births had decreased further. In addition, there had also been a significant
increase in folic acid intake in the Irish diet as a result of increased voluntary
fortification by food producers in recent years. In the interim period in which
fortification is postponed, further monitoring of folic acid supplement intake and rate
of NTD would take place to see if the situation had further changed. The report of the
implementation group is available via the link:
http://www.fsai.ie/assets/0/86/204/cc3c2261-7dc8-4225-bf79-9a47fbc2287b.pdf
Health Education Initiatives The Health Promotion Unit of the Irish Department of Health and Children has
undertaken much of this work at a national level. A folic acid promotional campaign
has been in operation since the official recommendations on folic acid came into
being in 1993. There are periodic national media campaigns prompting folic acid
supplement intake in women of child-bearing age. The Health Promotion Unit of the
Irish Department of Health has undertaken much of this work at a national level. At a
more local level, health promotion units and public health departments in the regions
promote folic acid through a variety of channels, generally on an on-going basis. The
2006 Report of the National Committee on Folic Acid Food Fortification
recommended the launch of a National Health Promotion Programme in relation to
all aspects of folic acid promotion. The details are available in the Report.2
Folic Acid Knowledge and Uptake There have been studies on folic acid awareness and uptake since 1995. The table
below summarizes the results of studies of women attending their first ante-natal visit
in maternity hospitals in Dublin. 3-9 The sample sizes in the studies from 1996-2000
were of 300 respondents each, using the same questionnaire, with core questions as
shown in the table. These studies mainly asked about daily folic acid tablet intake,
without explicitly asking about vitamin intake. The table below shows that since
1998, almost all mothers have heard of folic acid; and by 2002, more than three
87
quarters knew that it could prevent NTD. However, less than 25% of women were
taking periconceptional folic acid by 1998 and this had not changed by 2002.
Studies of Folic Acid Knowledge and Uptake in Ireland 1996-2002
Year 1996 1997 1998 1999 2000 2001 2002
Heard of folic acid 54% 76% 88% 91% 92% 94% 95%
Knew folic acid can prevent spina bifida / NTD 21% 44% 57% 64% 67% 83% 77%
Took folic acid periconceptionally 6% 16% 21% 22% 18% 24% 23%
As it was expected that fortification would take place by 2008, further studies were
deferred. However, with the postponement of fortification in 2008, new studies of
folic acid supplement intake were planned with the first taking place in mid -2009.
Health Care Professionals Although there has not been a survey among health care professionals, it is likely
that virtually all are aware of the recommendations considering the high profile folic
acid promotion campaigns that have taken place, and the high level of knowledge
among women of child-bearing age, the source of which is frequently a health
professional.
Proportion of Pregnancies which are Planned The studies quoted in the above table have found that the proportion of women
planning their pregnancy has been stable from 1996-2002 at 40-45%.
Laws Regarding Termination of Pregnancy Termination of pregnancy is not legal in Ireland except in the most extreme
circumstances. It is never allowed because of fetal abnormality. The number of
women who may go abroad for terminations because of fetal abnormality is not
known.
88
References 1. Food Safety Advisory Board. (1998) The value of folic acid in the prevention of
Neural Tube Defects. Food Safety Advisory Board, Dublin
2. Food Safety Authority of Ireland, Department of Health and Children (2006) Report of the National Committee on Folic Acid Food Fortification, Food Safety
Authority of Ireland, Dublin,
3. Milner M, Slevin J, Morrow A, Fawzy M, Clarke T, McKenna P (1996). Sub-
optimal compliance with periconceptional folic acid in an Irish hospital population.
Irish Med Journal; Vol 89, No 1, pp 28-29.
4. Sayers G, Scallan E, Mc Donnell R, Johnson Z. (1997) Knowledge and use of
periconceptional folic acid among ante-natal patients. Irish Med Journal; Vol 90,
No 6, pp 236-238.
5. Sayers G, Hughes N, Scallan E, Johnson Z. (1997) A survey of knowledge and
use of folic acid among women of child bearing age in Dublin. Journal of Public
Health Medicine; Vol 19, No 3, pp 328-332.
6. McDonnell R, Johnson Z, Doyle A, Sayers G. (1999) Folic acid knowledge and
use among expectant mothers in 1997 - a comparison with 1996. Irish Medical
Journal; Vol 92, No 3, pp 296-299.
7. McDonnell R, Johnson Z, Doyle A, Sayers G. (1999) Determinants of folic acid
knowledge and use among antenatal women. Journal of Public Health Medicine;
Vol 21, pp 145-49.
8. O’Leary M, Mc Donnell R, Johnson H. (2001) Folic acid and prevention of Neural
Tube Defects in 2000: Improved Awareness – Low Periconceptional Uptake.
Irish Medical Journal; Vol 94, No 6, pp 180-182.
9. Ward M, Hutton J, Mc Donnell R, Bachir N, Scallan E (2004) “Folic Acid
Supplements to Prevent Neural Tube Defects: Trends in East of Ireland 1996-
2002. Irish Medical Journal; Vol 97 No 9, 274-6.
89
Ireland (Dublin and Cork&Kerry and SE Ireland): Total and Livebirth Prevalence Rates for Neural Tube Defects (all 3 registries together)
0
5
10
15
20
25
30
35
40
45
50
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
Ireland (Dublin and Cork&Kerry and SE Ireland): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
30
35
40
45
50
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Dublin Total prevalence Cork and Kerry Total prevalence SE IrelandLivebirth prevalence Dublin Livebirth prevalence Cork and Kerry Livebirth prevalence SE Ireland
90
Ireland (Dublin and Cork&Kerry and SE Ireland): Total and Livebirth Prevalence Rates for Spina Bifida (all 3 registries together)
0
5
10
15
20
25
30
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
Ireland (Dublin and Cork&Kerry and SE Ireland): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
30
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Dublin Total prevalence Cork and Kerry Total prevalence SE IrelandLivebirth prevalence Dublin Livebirth prevalence Cork and Kerry Livebirth prevalence SE Ireland
91
Ireland (Dublin and Cork&Kerry and SE Ireland): Total and Livebirth Prevalence Rates for Anencephaly (all 3 registries together)
0
2
4
6
8
10
12
14
16
18
20
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
Ireland (Dublin and Cork&Kerry and SE Ireland): Total Prevalence Rates for Anencephaly
0
2
4
6
8
10
12
14
16
18
20
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Dublin Total prevalence Cork and Kerry Total prevalence SE Ireland
92
Report on Periconceptional Folic Acid Supplementation for Italy This document was prepared and approved by the Scientific Committee of the Italian
Network for Folic Acid Promotion for the primary prevention of birth defects and the
Italian Registers of Congenital Malformations
Sebastiono Bianca, Fabrizio Bianchi, Anna Maria Castellazzi, Elisa Calzolari,
Francesco Giorgino Libero, Alberto Mantovani, Stefania Ruggeri, Gioacchino
Scarano, Gianfranco Tarsitani, Domenica Taruscio, Romano Tenconi, Giuseppe
Ugolini
Edited and co-ordinated by Amanda J. Neville
Folic Acid Supplementation Policy The Italian Network for Folic Acid Promotion for the primary prevention of birth
defects was established in 2004 with the aim to propose and agree
recommendations regarding folic acid supplementation. The Network brings together
research institutions, patient organizations, scientific societies, universities, doctors,
health personnel and other institutions in order to promote collaboration and share
strategies for action. The objectives of the Network, in addition to the main topic of
primary prevention of birth defects with folic acid, have been extended to include the
nutritional aspects and approaches to promote proper dietary intake of folate, in
agreement with the evolution of the subject at European and international level. The
network now involves over 200 members and is coordinated by the National Centre
for Rare Diseases (CNMR) of the Institute of Health (ISS). The summary recommendation on Folic Acid Supplementation Policy
was approved in November 2004 and is as follows:
It was recommended that all fertile women that plan a pregnancy, or do not actively
exclude the possibility, take at least 0.4mg a day of folic acid. It is fundamental that
it is taken starting at least a month before conception and for all of the first trimester
of pregnancy.
93
The recommendation, together with more details (why, how much, when, foot notes
explaining the choice, and a list of scientific publications that support the
recommendation) is accessible at http://www.cnmr.iss.it/
Every year since the birth of the Network a national workshop (now Congress) is
organized to present the activities and achievements in various fields: research on
genetic and environmental risk factors of malformations, epidemiological
surveillance, risk-benefit assessment of strategies to promote adequate folic acid
intake, communication and public information and training of health professionals. In
order to widen discussion and collaboration international experts have been invited
to participate.
Implementation The first major result of the Network is the production and dissemination of material
both scientific and informative available on the website www. iss.it / cnmr / folic acid.
The scientific documents capitalize the interdisciplinary nature of the Network, with
attention given to interactions between folate and other factors (genetic / food /
environmental) and the role of folate nutrition. The Italian Registers of Congenital
Malformations are developing a shared system of data collection and processing of
reports that will allow the longitudinal evaluation of the impact of prevention activities.
From the analysis of trends the registries show a declining trend in the prevalence of
malformations linked to folic acid, probably indicative of the effectiveness of
increased supplementation with folic acid. A positive relationship established with
the Ministry of Labour, Health and Social Policy ensures network activities have a
positive impact on medico-social services at the national level.
The 2009 edition of the conference was important in consolidating the messages, the
strategic objectives and collaborative relationships between institutions related to the
Network. Actions in progress include:
- research on genetic susceptibility factors (polymorphisms of genes and
microRNAs) involved in the pathogenesis of non-syndromic orofacial clefts, another
group of birth defects associated with folate levels in pregnancy
- identification of new horizons for example:
1) research on probiotic foods naturally rich in folate, as an alternative to products
fortified with synthetic folic acid;
94
2) the opportunity to expand the future objectives and activities of the network to give
an even broader scope for the prevention of birth defects through proper eating
habits and life
Folic Acid Supplements on Sale
As a result of the work of the Italian Network for the Promotion of Folic Acid for the
Prevention of Congenital Defects a 0.4mg tablet was registered, declared refundable
(Class A) and marketed. Monitoring what proportion of women use each type of
supplementation is difficult due to the fact that some are sold as prescription drugs,
others as over the counter preparations and yet others as multi vitamins or food
supplements. Results presented at the Network meeting in Rome on Oct 5 20071
report that while there is a positive trend towards the correct use of folic acid few
patients and doctors are aware of the correct dosage and timing.
Food Fortification Policy
Periconceptional supplementation is seen as the central element in a strategy that
also includes the increase of knowledge, promotion of dietary habits based on
scientific evidence and the exploitation of women's empowerment in the
management of personal health and life choices.
An unquestionable merit of the Network has been the ability to critically evaluate,
through the collection and updating of scientific data, risks and benefits of
widespread fortification of foods with folic acid. The Network has developed,
discussed and disseminated the scientific community's doubts about the safety of an
uncontrolled increase in intake of folic acid in the whole population, and in particular
on the possible effect of tumour promotion in the population over 60. The position of
the ISS and the Network has been reported by EFSA ESCO2 on fortification with folic
acid highlights the serious gaps in knowledge that make it difficult to evaluate risk-
benefit and impose an attitude of caution
A study of folate intake in many sections of the Italian population is underway. The
results will serve as a basis for planning communication activities and promotion and
assessing the possibility of voluntary fortification of certain products.
95
Health Education Initiatives The Italian Network for the promotion of Folic acid in congenital malformation
prevention remains the coordinating body for health education initiatives. An
intensive communication work program has included the production and distribution
of brochures, posters and pamphlets at the national level, available at the Network’s
website http://www.iss.it/cnmr .
Recent initiatives include:
• The commitment of the associations of social and health workers, in particular,
the activities of the spontaneous movement of Italian Pharmacists to involve
pharmacists in promoting folic acid supplementation and the association of
obstetricians in non-hospital training of medical personnel. These activities
should be extended beyond the pilot projects, enhancing national coverage:
currently only fifteen provinces are actively involved as volunteers.
• NHS staff training, at national and local level in gynaecology and obstetrics and
food-nutrition areas, through active collaboration of the network and co-
ordination by CNMR. The on line course has seen a broad and active
participation (20 tutors and 1300 participants).
• Projects specifically aimed at the promotion of correct dietary habits in
adolescents at the national level (eg "Folate: building blocks for life")
• Participation of associations the campaign "I can not conceive life without folic
acid," sponsored in May by ASBI in collaboration with COOP Italy with the aim of
conveying the message of supplementation "in everyday life" spreading the
recommendation in Italian supermarkets
Knowledge and Uptake about Folic Acid
The percentage of Italian women who take folic acid in the periconceptional period
has increased markedly, but focus on the weakest members of society is needed.
The correct intake of folic acid in Italian women is now 13 to 33%, a considerable
advance from less than 5-10% in 2004-5 (data from the project "The Birth Pathway:
promotion and quality assessment of operating models ", coordinated by M.
Grandolfo, ISS). Progress is still insufficient and action plans are needed for more
effective communication and greater reach.
96
Proportion of pregnancies which are planned A pilot study on 200 women in 2005 showed 61% had planned their pregnancies3
This is in line with previously reported data giving 63% of pregnancies in Italy as
planned.4 Laws Regarding Termination of Pregnancy Voluntary termination of pregnancy became legal in Italy in 1984. Termination due to
a congenital anomaly is usually performed until gestational age of 23-24 weeks. A
psychiatric report is required. Termination of pregnancy is allowed only in NHS
hospitals, not in private clinics.
References:
1. Annual Workshop Italian Network for the Promotion of Folic Acid and
Prevention of Congenital defects, Istituto Superiore di Sanità. Rome 5
October 2007. Abstracts book.:La promozione dell’uso dell’acido folico:
effetti e difetti. Spina F et al. ISTISAN Congressi 07/C6.
2. ESFA ESCO Report on Analysis of Risks and Benefits of Fortification of
Food with Folic Acid issued 6 October 2009 http://www.efsa.europa.eu/cs/BlobServer/External_Rep/sco_esco_wg_folic_
acid_report_en,0.pdf?ssbinary=true
3. Grandolfo M. Conoscenze, attitudini e comportamenti riguardo l’acido folico.
Indagine pilota The Italian Network for the promotion of Folic acid in
congenital malformation prevention annual meeting (Dec5 2006)
www.iss.it/binary/acid/cont/Grandolfo.1167212437.pdf
4. Castiglioni M, Dalla Zuanna G, Loghi M. Planned and Unplanned Births and
Conceptions in Italy 1970-1995. European Journal of Population 17:3 207-233
(Sept 2001)
97
Italy (Emilia Romagna, North East Italy, Campania and Tuscany): Total and Livebirth Prevalence Rates for Neural Tube Defects (all 4 registries together)
0
2
4
6
8
10
12
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
Italy (Emilia Romagna, North East Italy): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
1
2
3
4
5
6
7
8
9
10
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Emilia Romagna Total prevalence NE Italy
Livebirth prevalence Emilia Romagna Livebirth prevalence NE Italy
98
Italy (Campania and Tuscany): Total and Livebirths Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
16
18
20
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Tuscany Total prevalence CampaniaLivebirth prevalence Tuscany Livebirth prevalence Campania
Italy (Emilia Romagna, North East Italy, Campania and Tuscany): Total and Livebirth Prevalence Rates for Spina Bifida (all 4 registries together)
0
1
2
3
4
5
6
7
8
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
99
Italy (Emilia Romagna, North East Italy): Total and Livebirth Prevalence Rates for Spina Bifida
0
1
2
3
4
5
6
7
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Emilia Romagna Total prevalence NE ItalyLivebirth prevalence Emilia Romagna Livebirth prevalence NE Italy
Italy (Campania and Tuscany): Total and Livebirth Prevalence Rates for Spina Bifida
0
2
4
6
8
10
12
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Campania Total prevalence TuscanyLivebirth prevalence Campania Livebirth prevalence Tuscany
100
Italy (Emilia Romagna, North East Italy, Campania and Tuscany): Total and Livebirth Prevalence Rates for Anencephaly (all 4 registries together)
0
0,5
1
1,5
2
2,5
3
3,5
4
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
Italy (Emilia Romagna, North East Italy, Campania and Tuscany): Total Prevalence Rates for Anencephaly
0
1
2
3
4
5
6
7
8
9
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Emilia Romagna (IT) North East Italy (IT) Campania (IT) Tuscany (IT)
101
Report on Periconceptional Folic Acid Supplementation for Malta Dr Miriam Gatt
Folic Acid Supplementation Policy In Malta an official policy regarding increasing folate in the diet was introduced in
1994. The policy advises that pregnant women and women intending to become
pregnant should increase their intake of foods rich in folate. This is a Department of
Health Circular No. 36/94
Food Fortification Policy There is no official food fortification policy and none is currently being planned.
However, a wide variety of imported fortified cereals and malted drinks are available.
Fortified breads are not readily available.
Health Education Initiatives
No official Department of Health Promotion campaigns directed at periconceptional
folic acid supplementation have been undertaken but GPs, gynecologists, midwives
and organised antenatal courses inform women of the benefits of folic acid. The
official dietary policy mentioned above was aimed to inform and educate health
professionals.
Folic Acid Awareness and Uptake A study regarding folic acid awareness in Maltese mothers was undertaken between
October 1999 and February 2000 (Gatt 2000). The results were published as a
report from the Malta Congenital Anomalies Register. Of the mothers interviewed in
the study, 72% had known that folic acid was important in pregnancy. 15% of
mothers took folic acid supplementation prior to pregnancy; another 59% of mothers
started folic acid after conception but before 12 weeks of gestation. 35% said that
they had changed their diet during pregnancy, increasing their folate intake.
Proportion of Pregnancies which are Planned No information currently available
Laws Regarding Termination of Pregnancy In Malta, termination of pregnancy is not legal.
102
References: Gatt M (2000) Periconceptional Folic Acid Supplementation in Malta, in 'Half Yearly
Report of Malta Congenital Anomalies Register July – December 1999, Malta
Congenital Anomalies Registry, Department of Health Information. [Available:
http://www.sahha.gov.mt/showdoc.aspx?id=43&filesource=4&file=hyjuly-
dec1999.pdf )
Malta: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
103
Malta: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Malta: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
104
Report on Periconceptional Folic Acid Supplementation for the Netherlands Dr HEK de Walle
Folic Acid Supplementation Policy In 1993 the official Dutch advice was that all women wishing to become pregnant
should take a folic acid supplement of 0.5 mg per day. Women with a previous NTD
affected pregnancy are advised to consume 5 mg per day. The official status for that
policy was the Ministry of Health Welfare and Sports1.
Food Fortification Policy Since 1996 different types of food have been fortified with vitamins and minerals in
the Netherlands. For example, extra calcium is added to milk and some vitamins are
added to (expensive brands of) marmalade. Initially, folic acid was not one of the
vitamins added to food because of the risk of masking a vitamin B12 deficiency.
In 2001, the Dutch Health Council issued a report2 which did not advise fortification
of staple foods such as flour, but advised fortification of products that could be
specifically aimed at the target population (ie. women who want to become
pregnant). No suggestions were made as to what these products should be or what
the recommended amount of folic acid to be added to these products would be.
For the last couple of years folic acid has been added to some cereals such as
Kellogg’s cornflakes and to some margarines. This has been made possible due to a
recent change in regulations regarding micronutrients after the advocate-general of
the European Court of Justice decided that fortification of special foods must be
allowed in the Netherlands.
In 2008 a new group of the Dutch Health Council will look at the issue of fortification
again. A point In favour of fortification is that 60-70% of all the people in the
Netherlands do not reach the 200-300 micrograms of folate per day that is
recommended.
105
Health Education Initiatives
A campaign was aimed at all women of childbearing age but with a special emphasis
on reaching women with a low socio-economic status. General targets of the
campaign were that 70% of women planning a pregnancy should know the
recommended period to use folic acid and that 65% of women who knew of the
advice before pregnancy should use folic acid during the entire recommended
period 3. This campaign was carried out in 1995.
Currently, the Dutch Ministry of Health are running four projects concerning folic
acid. Three of them are interventions: in the pharmacy, via the midwives and ‘well
baby clinics”. The fourth project is to give, on a large scale, as much information as
possible about folic acid. This includes digital and written information and is carried
out by the Dutch “Erfo centrum” (Centre for congenital and hereditary diseases). The
website on folic acid is: http://www.slikeerstfoliumzuur.nl/
Folic Acid Awareness and Uptake Figure 1 The use of folic acid during the entire advised period according to
educational level
The level of knowledge about folic acid increased satisfactorily in the five years after
the campaign. However, the percentage that used it in the advised period did not
follow the same trend. Figure 1 shows how socio-economic status is related to use of
folic acid during the last five years in which we did the four surveys 4-8. It is clear that
05
101520253035404550
1995 1996 1998 2000Survey
perc
enta
ge
high educationmiddle educationlow education
106
the goal of the campaign that the 65% of the women who were aware of the folic acid
advice before their pregnancy should use folic acid during the entire recommended
period is not reached in any of the surveys (36% of women surveyed in 1999 used
folic acid during the entire recommended time). Socio-economic differences with
respect to knowledge and use of folic acid remained statistically significant in all the
surveys. This means that another goal of the public campaign, the reduction of socio-
economic differences with respect to the use of folic acid, was not reached. It is
disappointing to conclude this was also true in the regions where an extra
intervention was made to reach women with a low education. Striking examples are
the billboards with the folic acid message, which were placed in public areas and in
buses. The more highly educated women remembered this information much better
than the group for whom it was intended.
In a more recent study, 9 we evaluated women’s awareness of and use of folic acid
in 2003 and looked at the trend of folic acid use among pregnant Dutch women
between 1995 and 2003 with regard to socio-economic status (SES). Method: We
conducted 2-yearly cross-sectional studies among pregnant women who filled in a
questionnaire during the first or second antenatal visit. The highest achieved level of
education was taken as a proxy for SES. Results: In 2003 the general level of folic
acid awareness was high but with significant differences relating to SES; a quarter of
the lower educated women did not know about folic acid before pregnancy. Of the
subjects with a lower SES, 20% knew the correct period of use compared with nearly
50% in the higher SES group. Worryingly, the reported correct use of folic acid
among the lower educated women has actually decreased over the past 3 years
(22% in 2003), while it has increased for the higher SES groups (59% in 2003),
implying larger discrepancies in health between the lower and higher SES groups.
Conclusion: In 2003, 8 years after a mass media campaign, awareness and use of
folic acid were increased considerably in comparison with the start of the campaign.
However, differences in knowledge and use of folic acid with respect to the level of
education had increased by 2003. A once-only campaign has a short-term effect
especially for lower educated women. Strategies to promote folic acid use in daily
structural health care systems are needed.
107
Pharmacists’ Role in Folic Acid Education About 70% of Dutch women use oral contraceptives sometime before the first
pregnancy. For this reason they visit their pharmacy regularly, which provides a great
opportunity to educate them about folic acid. In 2002, a pilot study was performed to
investigate the feasibility of a proactive intervention through pharmacies and the
attitude of the target population towards this education 10 . The study showed the
intervention was feasible and the target population was positive about the
information received. Evaluation of the intervention showed that the use of folic acid
was higher among women using the intervention pharmacies compared to those
using the reference pharmacies. The difference was more marked among women
with a first pregnancy11. In view of the success of this intervention, it was decided to
implement it more widely.
Proportion of Pregnancies which are Planned The Netherlands has a high percentage of planned pregnancies12. In our surveys the
percentage of planned pregnancies was high (around 85%) and it was not related to
the socio-economic status of the respondents. However, the concept of “planned” in
the way the respondents are using it might be different from the way it is interpreted
by researchers.
Our study shows that in the Northern Netherlands, in 2000, women were aware of
the importance and the correct time frame of using folic acid. However, not all of
them took folic acid in the periconceptional period. This was not because of a
negative attitude towards taking folic acid but, according to the most often mentioned
reason, because although the pregnancy was planned they conceived sooner than
expected.
Laws Regarding Termination of Pregnancy In the Netherlands, termination of pregnancy for fetal abnormality is allowed until 24
weeks of pregnancy. Parents have to be informed about all the facts concerning
their situation and have the sole power to decide whether to terminate the pregnancy
in a controlled facility. After 24 weeks of pregnancy, termination is only permitted in
the case of a fetus with a disorder not compatible with life and a woman who has
major mental problems with carrying on with the pregnancy. The decision has to be
108
reviewed by a multidisciplinary committee and has to be reported to the counsel for
the prosecution.
References:
1. Gezondheidsraad/ Voedingsraad (1993). Continued advice concerning folic
acid use in relation to neural tube defects. [Vervolgadvies inzake
foliumzuurvoorziening in relatie tot neuraalbuisdefecten.]. Den Haag,
Voorlichtingsbureau van de Voeding.
2. Health Council of the Netherlands (2000). Risks of folic acid fortification.
2000/21, 5-48. 15-11, The Hague.
3. Voorlichtingsbureau voor de voiding (1994). Prevention of neural tube defects
by supplementation of folic acid [preventie van neuraalbuisdefecten door
middel van foliumzuur (suppletie)]. Praeventiefonds voorstel, editor. Den
Haag.
4. de Jong- van den Berg LTW, de Walle H.E.K., van-der-Pal-de BK, Buitendijk
SE, Cornel MC (1998). Increasing awareness of and behaviour towards
periconceptional folic acid consumption in The Netherlands from 1994 to
1995. Eur J Clin Pharmacol, Vol 54, No 4, pp 329-331.
5. de Walle HEK, van der Pal KM, de Jong- van den Berg LTW, Jeeninga W,
Schouten JS, de Rover CM et al (1999). Effect of mass media campaign to
reduce socioeconomic differences in women's awareness and behaviour
concerning use of folic acid: cross sectional study. BMJ, Vol 319, No 7205, pp
291-292.
6. de Walle HEK, de Jong- van den Berg LTW, Cornel MC (1999).
Periconceptional folic acid intake in the northern Netherlands. Lancet Vol 353,
No 9159, pp 1187.
7. de Walle HEK, van der Pal KM, de de Jong-van Den Berg LTW, Schouten J,
de Rover CM, Buitendijk SE et al (1998). Periconceptional folic acid in The
Netherlands in 1995. Socioeconomic differences. J Epidemiol Community
Health, Vol 52, No 12, pp 826-827.
8. de Walle HEK, de Jong- van den Berg LTW (2002). Insufficient folic acid
intake in the Netherlands: what about the future? Teratology Vol 66, No 1, pp
40-43.
109
9. de Walle, H.E.K., de Jong-van den Berg, L.T.W, Growing Gap in Folic Acid
Intake with Respect to Level of Education in the Netherlands. Community
Genet 2007;10:93-96 (DOI:10.1159/000099086)
10. Meijer WM, Smit DJ de, Jurgens RA, Jong-van den Berg LTW de.
Pharmacists role in awareness about folic acid: the process of introducing an
intervention in pharmacy practice. Int J Pharm Pract 2004;12:29-35
11. Meijer WM, Smit DJ de, Jurgens RA, Jong-van den Berg LTW de. Improved
periconceptional use of folic acid after patient education in pharmacies –
promising results of a pilot study in the Netherlands. Int J Pharm Pract (in
press)
12. Vennix P (1990). De pil en haar alternatieven: ervaringen van de Nederlandse
vrouw met de pil en andere vormen van conceptie. 6. Delft, Eburon. NISSO
Studies.
Northern Netherlands: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
110
Northern Netherlands: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Northern Netherlands: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
111
Report on Periconceptional Folic Acid Supplementation in Norway Dr Anne Kjersti Daltveit
Folic Acid Supplementation Policy The official folic acid supplementation policy in Norway, issued in the spring of 1998
by the National Council on Nutrition and Physical Activity, is that women who are
planning a pregnancy or who may become pregnant are recommended to have a
total intake of at least 400 µg of folic acid per day. Since an intake of 400 µg through
the diet is unlikely to be achieved by many women, and since there are reasons to
believe that supplementation is more efficient than diet in reducing the risk, the
practical recommendation is to take a folic acid supplement of 400 µg per day. The
supplementation should begin prior to the first month before conception and continue
until 2-3 months of gestation. Women with an increased need for folic acid due to disease or medication (eg anti-
epileptic medication), and women with neural tube defects in their own or their
partner's family, are recommended to confer with their doctor about a supplement of
more than 400 µg per day. The supplementation should begin prior to the first month
before conception and continue until 2-3 months of gestation.
Women who have previously had a fetus with a neural tube defect as well as women
who themselves or their partner have a neural tube defect are recommended to take
4 mg of folic acid supplement per day. The supplementation should begin prior to the
first month before conception and continue until 2-3 months of gestation.
After the first 2-3 months of pregnancy, pregnant and breastfeeding women are
recommended to have a total intake of folic acid of 400 µg per day. It is suggested
that a common level of dietary intake of folic acid among Norwegian women in the
child-bearing age is about 200 µg per day. It is therefore recommended that women
continue with a folic acid supplement of 200 µg per day during the last 6 months of
pregnancy and during the breastfeeding period.
112
Women of child-bearing age are recommended to have a dietary intake of folic acid
of 300 µg per day. With the exception of recommendations regarding pregnancy and
breastfeeding, women of child-bearing age are not recommended to take folic acid
supplementation.
The above recommendations were issued in the spring of 1998 by the National
Council on Nutrition and Physical Activity (1998). Before 1998, the official
recommendations were those issued by the Board of Health in February 1993.
These first recommendations did not recommend the use of supplements for any
women other than those at risk of recurrence, but stated that women of child-bearing
age should consume 400 µg through their diet.
Food Fortification Policy A working group was established in 1997 by the National Council on Nutrition and
Physical Activity to suggest recommendations and means of increasing the intake of
folic acid among women of child bearing age. The working group’s recommendation
was that food fortification with folic acid should not be implemented; it maintained
that women should be recommended to have a supplementary intake of folic acid in
the periconceptional period (Rapport nr. 1/1998). This decision was reviewed by a
working group appointed by the Norwegian Directorate for Health and Social Affairs.
Their report was published in December 2004. It found that the policy of
recommending periconceptional folic acid supplementation had not yielded
satisfactory results. It recommended that consideration be given to mandatory
fortification with folic acid of a staple food.
Health Education Initiatives An official Health Education Initiative began in Norway in autumn 1998 to inform
women about the role of folic acid in reducing the risk for neural tube defects. The
Norwegian Agency for Health and Social Welfare (formerly National Council on
Nutrition and Physical Activity) has a public web site (1998). At the web site there is
information on the occurrence of neural tube defects in Norway, recommended daily
intake of folic acid, folate content in different foods, when to take supplementation of
folic acid in connection with pregnancy, potential side effects related to high intake of
113
vitamin A through multivitamin supplementation, and needs of special groups such
as epileptic women.
Leaflets published by the Norwegian Agency for Health and Social Welfare (formerly
National Council on Nutrition and Physical Activity) are distributed to women by
general practitioners, specialists in gynaecology and obstetrics, midwives, health
care centres for mother and child, drugstores, and pharmacies. Also posters and
post cards are distributed, and there have been advertisements in women's
magazines and other relevant magazines.
Health personnel are requested to inform women about folic acid and pregnancy at
the time of giving guidance on contraceptive devices, doing pregnancy tests,
removing an intrauterine device, selling of pregnancy tests, and selling of
contraceptive devices. The Norwegian Agency for Health and Social Welfare has
distributed a guide for health personnel with these items.
The national recommendations for periconceptional folic acid supplementation are
now included in the updated official guidelines for antenatal care in Norway Folic Acid Awareness and Uptake Following the recommendations issued in the spring of 1998, a random
sample of 1500 Norwegian women of reproductive age was selected for study of
their awareness of recommendations regarding folic acid supplementation and of
their uptake of the advice. Among the 1500 women, telephone interviews were
carried out with 1146 women in the autumn of 1998. (Vollset & Lande 2000) The
study was repeated in 2000. (Daltveit ,Vollset , Lande , Oien, 2004)
The folic acid recommendation issued by the National Council on Nutrition and
Physical Activity in March 1998 was known by 22% of women in 1998 increasing to
32% in 2000. Supplementation with folic acid before conception or early in
pregnancy, when that pregnancy was less than one year ago, was reported by 10%
of women in 1998 increasing to 46% in 2000. Intention to follow the
recommendations on folic acid supplementation in a future pregnancy was reported
by 56% of women in 1998 increasing to 68% in 2000. Intention to follow
114
recommendations on consumption of folate rich food in a future pregnancy was
reported by 75% of women in 1998 and again in 2000. The women were also asked
about other vitamin supplementation. Supplementation of other vitamins or minerals
before or early in pregnancy among women in whom the last pregnancy was less
than one year ago, was reported by (numbers for 2000 in parenthesis) 57% (79%)
for any vitamin or mineral supplementation, 29% (30%) for multivitamins, 5% (11%)
for vitamin B, 28%(20%) for iron, and 21% (32%) for cod liver oil.
A further study of folic acid supplement use among pregnant women: the Norwegian
Mother and Child Cohort Study was published in 2006 (Nilsen et al 2006). In addition
to a description of use of folic acid supplementation before and throughout
pregnancy, socio-demographic differences in use were studied. An important finding
was that most women started folic acid supplementation too late with respect to the
prevention of neural tube defects.
A study of epileptic women found that women of childbearing age treated with anti
epileptic drugs received folic acid supplementation, particularly those who were
taking P450-inducing anti epileptic drugs. ( Kampman 2007)
Proportion of Pregnancies which are Planned
There is little knowledge in Norway about the proportion of pregnancies that are
planned. In the Norwegian Mother and Child Cohort Study (www.fhi.no ), preliminary
unpublished data suggest that 76% of the pregnancies were planned. However, the
response rate was low, and the true proportion of pregnancies that were planned is
thought to be somewhat lower, somewhere between 50% and 75%.
Laws Regarding Termination of Pregnancy Induced abortion is legal at a woman’s request up to 12 completed weeks of
gestation. Induced abortion is legal on specified medical and social indications above
12 completed weeks and up to18 completed weeks, and the decision is made by an
abortion board. After 18 completed weeks, induced abortion is legal if the pregnancy
represents a serious risk to the mother, or if the fetus suffers from a condition
incompatible with life. In those cases there is no gestational age limit.
115
References
1. Anbefalinger og virkemidler for økt folatinntak blant kvinner i fertil alder.
Rapport nr. 1/1998. Oslo:Statens ernæringsråd, 1998.
2. Daltveit AK,Vollset SE, Lande B, Oien H. Changes in knowledge and
3. attitudes of folate, and use of dietary supplements among women of
4. reproductive age in Norway 1998-2000. Scand J Public Health.
5. 2004;32(4):264-71.
6. Kampman MT. Folate status in women of childbearing age with
epilepsy.Epilepsy Res. 2007;75:52-6. Epub 2007 May 21.
7. Nilsen RM, Vollset SE, Gjessing HK, Magnus P, Meltzer HM, Haugen M,
Ueland PM. Patterns and predictors of folic acid supplement use among
pregnant women: the Norwegian Mother and Child Cohort Study. Am J Clin
Nutr. 2006;84:1134-41.
8. Sosial- og helsedirektoratet, Avdeling for primærhelsetjenester. Retningslinjer
for svangerskapsomsorgen, ISBN 82-8081-067-6 05/2005
9. Statens råd for ernæring og fysisk aktivitet (National Council on Nutrition and
Physical Activity), spring 1998. Website: www.folat.org
10. Statens helsetilsyn (Norwegian Board of Health): Tiltak som kan redusere
forekomst av nevralrørsdefekter. Rundskriv IK-4/93.
11. Vollset SE and Lande B, Knowledge and attitudes of folate, and use of dietary
supplements among women of reproductive age in Norway 1998. Acta
Obstet Gynecol Scand. 2000 Jun;79(6):513-9.
116
Norway: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
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er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Norway: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
117
Norway: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
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0 bi
rths
Total prevalence Livebirth prevalence
118
Report on Periconceptional Folic Acid Supplementation for Poland Dr Anna Latos-Bielenska
Folic Acid Supplementation Policy In 1997 there was a nation wide government program regarding periconceptional
folic acid supplementation. The program “Primary Prophylaxis of Neural Tube
Defects”, was headed by Professor Zbigniew Brzezinski, from the Department of
Epidemiology, Institute of Mother and Child, Warsaw. The original recommendation
was that all women of child bearing age should take 0.4 mg of folic acid daily and
that women planning a pregnancy should take 0.8 mg daily. The current
recommendation is altered, and all women of child bearing age, including those
planning a pregnancy, are advised to take 0.4 mg of folic acid daily.
Food Fortification Policy Food fortification is planned for the Lublin Province in which there are approximately
30,000 births per year.
Health Education Initiatives
An educational program is aimed at women, health care professionals and children
over fifteen years of age.
The Polish Registry of Congenital Malformations has arranged that mothers of
children with congenital malformations are sent a letter with information about the
indications for genetic counselling and about the benefit of folic acid. Mothers
delivering a child with a NTD are informed about the need to take 4 mg folic acid/day
while trying to conceive a pregnancy.
There are web sites on folic acid:
www.kwasfoliowy.pl/
www.genetyka-ginekolog.pl
Knowledge and Uptake of Folic Acid Folic acid supplementation was taken by 15% of women aged 18-45 in 1999 and by
19% of women aged 18-45 in 2000; by 11% of non-pregnant women aged 18-45 in
1999 and by 13% of non-pregnant women aged 18-45 in 2001; by 9% of women
119
under 20 years of age in 1999 and by 16 % of women under 20 in 2001. Thus, folic
acid supplementation rates had gone up for all three categories within the space of
two years. 57% of women took other vitamin supplements. (Primary Prophylaxis
2000)
Data has since been collected by the Polish Registry of Congenital Malformations. It
has been not published yet but has been presented at conferences in Poland. The
proportion of women taking folic acid during pregnancy was found to be 64% in
2003, 63% in 2004 and 70% in 2005. The proportion of women taking folic acid
before pregnancy was found to be 5.5% in 2003, 7.4% in 2004, 10.6% in 2005.
Proportion of Pregnancies which are Planned The proportion of pregnancies which are planned in Poland is low.
Laws Regarding Termination of Pregnancy In Poland termination of pregnancy is allowed in the following instances:
1. the pregnancy is dangerous for the life of the mother (up to 12 weeks
gestational age).
2. the pregnacy is the result of a crime (up to 12 weeks gestational age)
3. the fetus is seriously and irreversible damaged (up to 23 weeks
gestational age)
The gestational age limit for termination of pregnancy is under 23 weeks.
References
1. Brzeziński Z. [Primary prevention program for neural tube defects in Poland]
[Article in Polish] Med Wieku Rozwoj. 1999 Oct-Dec;3(4):503-8.
2. Czochańska J, Lech M. [Prevention of neural tube defects. An important
health and social problem] [Article in Polish] Przegl Lek. 1998;55(4):174-8.
3. Gos M, Sliwerska E, Szpecht-Potocka A. Mutation incidence in folate
metabolism genes and regulatory genes in Polish families with neural tube
defects. J Appl Genet. 2004;45(3):363-8.
4. Kuna A, Kazimierczak M, Sipiński A, Machura M, Selwet M, Sioma-
Markowska U. [Assessment of mass-scale primary prevention of nervous
system defects] [Article in Polish] Wiad Lek. 2004;57 Suppl 1:178-82.
120
5. Lech M. [Prevention using folic acid--a good method for reduction of neural
tube defects in Poland] [Article in Polish] Przegl Lek. 1998;55(6):334-6.
6. Mierzejewska E, Brzezinski ZJ, Mazur J. [Basic principles of evaluation of
neural tube defects primary prevention programme] [Article in Polish] Med
Wieku Rozwoj. 2000;4(4 Suppl 1):129-53.
7. Perenc L, Mach-Jamińska A. [The primary prophylaxis of neural tube defects
in the Podkarpacian region] [Article in Polish] Przegl Lek. 2006;63(8):606-9.
8. Program of primary prophylaxis of neural tube defects in 1997-2001, Institute
of Mother and Child, Warsaw 2000
9. Program of primary prophylaxis of neural tube defects, Institute of Mother and
Child, Warsaw, 2002.
10. Sawulicka-Oleszczuk H, Kostuch M. [Influence of folic acid in primary
prevention of neural tube defects] [Article in Polish]. Ginekol Pol. 2003
Jul;74(7):533-7.
11. Szumska A, Mazur J. [Evaluation of knowledge, attitudes and practice in
healthy women of childbearing age concerning prophylactic folic acid--
preliminary report]
12. [Article in Polish] Med Wieku Rozwoj. 1999 Oct-Dec;3(4):509-20.
13. Zbigniew Brzezinski, Report on realization of program of primary prophylaxis
of neural tube defects in 1997-2001.
121
Poland: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Poland: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Wielkopolska Total prevalence Poland (apart from Wielkopolska)Livebirth prevalence Wielkopolska Livebirth prevalence Poland (apart from Wielkopolska)
122
Poland: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Poland: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Wielkopolska Total prevalence Poland (apart from Wielkopolska)Livebirth prevalence Wielkopolska Livebirth prevalence Poland (apart from Wielkopolska)
123
Poland: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Poland (Wielkopolska and the rest of Poland) Total Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Wielkopolska Total prevalence Poland (apart from Wielkopolska)
124
Report on Periconceptional Folic Acid Supplementation for Portugal Dr Paula Braz and Carlos Matias Dias
Folic Acid Supplementation Policy In March 1998 there was a recommendation from the General Directorate of Health
(guideline number 2/DSMIA) to all health care professionals, to inform the
childbearing population about the importance of folic acid. There was no information
about dosage.
In January 2006, these recommendations were updated by the General Directorate
of Health (guideline number 2/DSMIA). All health professionals are instructed to
inform the childbearing population to start folic acid at least two months before
stopping contraception.
Folic acid supplements are available on prescription in Portuguese pharmacies:
0.4mg dose - multivitamin pill (Centrum, Prenatal)
0.3mg -1mg dose – combination with ferritin
5mg dose - monopreparation pill (Folicil, Acfol, Lederfoline, Raycept)
Food Fortification Policy There is no food fortification policy, but one of the most important commercial firms
in Portugal for milk products (Mimosa) decided five years ago to fortify milk with
50µg/100ml of folic acid.
Health Education Initiatives The Portuguese Association, Spina Bifida and Hydrocephalus, (ASBIHP) initiated an
educational project to promote the importance of folic acid in the prevention of NTD.
This project, which took place during 2003 and 2004, was targeted at universities
and health professionals. The same association also conducts a project called “Olá
Bebé” (Hello Baby) to support parents with a new baby with NTD.
The Internet site of ASBIHP has information on folic acid;
www.asbihp.org
125
Knowledge and Uptake of Folic Acid Machado and Feijóo, in their study (2006)1, found that 77.5% of women aged 24-44
years old knew about folic acid, but only 20% were able to describe folic acid as an
effective method to reduce NTD. 15.4% of all respondents knew that
supplementation with folic acid should begin before conception.
In 2005, Braz 2 found an increase in the proportion of women taking folic acid prior
to pregnancy since 1998. In 2005, 23.9% (CI 95% 14,0;33,8) of women in her study
took folic acid prior to pregnancy. There was a significant association (p<0,001)
between appropriate intake and the pregnancy being planned.
Proportion of Pregnancies which are Planned In one survey,3 54.5% of all women surveyed who had ever been pregnant reported
having consulted an MD while preparing for their last pregnancy.
Laws Regarding Termination of Pregnancy Termination of pregnancy is legal in Portugal until 24 weeks gestation for major
congenital anomalies, rape, and risk to the mother’s health. It is legal up to term if
an anomaly is incompatible with life. There is a technical committee in each
obstetric unit in which terminations are performed which decides in each case if the
procedure is legal.
In April 2007, a new law was passed allowing termination of pregnancy until 10
weeks of gestation if a woman does not wish to be pregnant. This law did not affect
the regulations regarding termination of pregnancy due to major congenital
anomalies, rape, and risk to the mother’s health.
References
1. Machado A, Feijóo M. Ácido fólico e anomalias congénitas: conhecimentos da
população portuguesa. Revista Portuguesa de Clínica Geral 2006:22:149-60.
2. Braz P. Importância do suplemento com ácido fólico: nível de adesão nas
mulheres em idade fértil (MSc Public Health Thesis, National School of Public
Health, Lisbon, 2005. not published)
126
3. PORTUGAL, Health Interview Survey 2005/2006. National Institute of Health,
Lisboa, 2007
Portugal (South Portugal): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Portugal (South Portugal): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
127
Portugal (South Portugal): Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
128
Report on Periconceptional Folic Acid Supplementation for Slovenia Dr Ksenija Ogrizek Pelkič
Folic Acid Supplementation Policy In Slovenia, there is no official government recommendation for periconceptional
folic acid supplementation, but a recommendation was published by the Slovenian
Association for Perinatal Medicine in 1998. They recommended that all women
wishing to become pregnant should take periconceptional folic acid supplementation
of 0.4 mg per day before conception. Women who were already pregnant should
start taking folic acid supplementation during the first four weeks of gestation and
continue until the 12th week. Women with increased risk of having a pregnancy with
a neural tube defect due to malabsorption, long-term use of certain medications,
diabetes mellitus or neural tube defects in relatives are recommended a folic acid
supplement of 4 mg per day until the end of pregnancy.
There is no funding for folic acid products during pregnancy; pregnant women have
to pay for it themselves.
Food Fortification Policy
There is no official food fortification policy in Slovenia. We have sent a letter to the
Minister for Health requesting that action towards fortification of a staple food with
folic acid be set in motion ( september 2007).
Health Education Initiatives There is no official health education initiative in Slovenia, but there are many
initiatives by the Slovenian Association for Perinatal Medicine. Leaflets addressing
women planning pregnancy have been published and distributed to general
practitioners, specialists in gynaecology and obstetrics, and
gynaecological/obstetrical departments of the Slovenian hospitals. There have been
no paper or television advertisements, but the issue has been covered in some
newspaper articles and in magazines concerning health, pregnancy and children.
Some Slovenian sites on the Internet are used to educate women about healthy
nutrition and about the importance of taking ample folic acid (www.med.over.net,
www.ringaraja.net). The initiative is still ongoing.
129
Knowledge and Uptake of Folic Acid In Slovenia a study was carried out and published in 2001 (1). This study found that
79% of the pregnant women questionned knew about folic acid, but only 7% were
aware of the benefits of supplementation. 52% of them were taking folic acid during
the last pregnancy. 27% took it before conception. Only 14% of all pregnant women
took folic acid correctly.
In 2007 we administered a questionnaire to pregnant women in a prenatal clinic in
the Maribor teaching hospital (unpublished data): 350 pregnant women completed
the questionnaire. 88% of the women were taking folic acid, but only 31.5% of them
during the appropriate periconceptional period. An increase was seen in the
proportion of women complying with the recommendation in the study period and this
coincided with the information campaign events.
Proportion of Pregnancies that are Planned
The proportion of pregnancies that are planned in Slovenia is unknown.
Laws Regarding Termination of Pregnancy
The national law is that up till 10 weeks of gestational age every woman may opt for
termination of pregnancy without special permission. After 10th week termination of
pregnancy for fetal anomaly can be performed after permission from a regional
committee (two doctors and one employee at the Social centre). The upper gestation
limit for fetal anomaly is not set.
References 1. Završnik S, Novak- Antolič Ž (2001) » Supplementation with folic acid
prevents neural tube defects. Situation in Slovenia« Preterm labour, delivery
and newborn: proceedings / VIII. Novakovi dnevi, Maribor; editor Živa Novak –
Antolič. Association for Perinatal Medicine. 177-184.
130
Report on Periconceptional Folic Acid Supplementation For Spain
Dr Isabel Portillo and Dr Blanca Gener
Folic Acid Supplementation Policy
In 2003, the Ministry of Health updated its advice regarding use of periconceptional
folic acid supplementation to reduce the risk of having a child affected with an NTD.
This is available in the web and links with other National Recommendations(1).
These recommendations are in line with the policy introduced in 2001 advising the
intake of folic acid prior to pregnancy: All women who are considering a pregnancy
and have no previous pregnancy affected by NTD should take 0.4 mg per day of folic
acid at least one month before conception and during the first three months of
pregnancy; Women planning a pregnancy who have already had a pregnancy
affected with NTD should take a dose of 4 mg per day of folic acid at least one
month before conception and during the first three months of pregnancy(2). However,
the 2003 document advises that more emphasis should be placed on dissemination
of information.
In the Basque Country, recommendations are included in the Health Promotion web-
page and also in all patient information leaflets for pregnant women, as well as
medical record(3).
The Spanish Society of Gynaecology and Obstetrics (SEGO) continues the
promotion of folic acid supplements in accord with international and national patterns
(daily dose of 0.4 mg in low risk and 4mg in high risk taken periconceptionally). Also
they recommend not using multivitamin tablets in order to achieve the desired doses
of folic acid, because in order to do this an excess of other vitamins (e.g. vitamins A
and D) might be taken, and this could be dangerous both for the fetus and the
mother.
131
Food Fortification Policy
At this time, there is no mandatory fortification of food with folic acid. However, there
is voluntary fortification of most breakfast cereals.
Knowledge and Uptake of Folic Acid Studies of Prevalence of folic acid intake
In Spain, the average daily intake of folic acid in the adult female population was
estimated to be 211.7 µg (108) by Aranceta et al, (1994)(4) in the Basque Country
and to be 392 µg (131) in Valencia Country (Vioque et al, 2000)(5). These studies
were based on the Nutritional Inquiry of 1994 and on blood tests. In the Basque and
Valencia countries, percentages of women who took the appropriate amount of folate
(400цg per day) were low (10% and 40% respectively). Also the observational study
of Ballesteros et al (1999)(6) in Cantabria Community found that only 12% of pregnant
women in the first trimester had optimum levels of serum folate. Population studies
done in Catalonia by Garcia et al (2002)(7) found that 12.9% women aged 18-34
years had sub optimal serum folate levels. More recently, Martinez-Frias et al
(2007) found that of 16,761 newly delivered women with non-malformed infants, 17%
took folic acid prior to conception, while a further 71% took it after conception. (8).
Studies of Prophylaxis Assessment
Study Design Intake of periconceptional folic acid supplements
Knowledge of benefits of folic acid
Recommendations
Gilbert et al (2000)(9)
Retrospective
651 mothers attended in Hospital
Mallorca
1998
4.5% of the prescribed preventions were sufficient and they were more frequent in private medicine (12%) than in public medicine (3.4%) (p= 0.036).
85.2 % of midwifes and 45.7% of gynaecologists recommended prophylaxis when the mother first attended the antenatal clinic or before (p<0.001).
Involvement of Gynaecologists, midwives, and Public institutions
132
Martínez-Frías et al(10 (2003)
Retrospective
Mothers of controls ECEMC database (1980-2002): 28522
Mothers of controls 2001 and first trimester 2002: 1338.
Spanish hospitals
Increased intake of folic acid since 1992 (80%).
2002 10.62% of women took folic acid prior to pregnancy.
Dosage higher (>4.5mg per day) than recommendations.
100% mothers with low educational level did not take any supplementation
More than 15% of mothers with high educational level took supplements of folic acid
Primary Care physician to be involved in prevention of NTD.
Cultural and social barriers to be addressed
Fortification of staple food such as flour.
García et al(11) (2003)
Observational
346 pregnant women in Madrid referred to hospital for delivery
1999-2000
17% (CI 95% 13.2-21.4) of women took periconceptional folic acid.
Appropriate intake was significantly associated with marital status and with prescription by primary care physician
no association with social or educational level
34% (CI 95% 29.2-40.1) of women were able to describe folic acid as efficacious method to reduce NTD
The role of Primary Care physician to prevent NTD
Gutierrez et al(12) (2003)
Observational
Sample of 928 pregnant women <35 years.
Economic analysis of prescription in 101 women
Zaragoza
Unknown period
15,4% of women took supplementation with folic acid correctly.
There was significant association (p<0,001) between appropriate intake and planned pregnancy.
2.4% of women took supplementation of multivitamins not recommended.
32% of women did not take any folic acid supplementation
no association with social or educational level.
72, 6% of women knew that periconceptional folic acid supplementation can prevent NTD
Prescription of commercial folic acid (400ц) supplement with sufficient B12 to prevent deficit of B12
Perez-Vázquez et al(13) (2003)
Observational
148 pregnant women in Pontevedra
Unknown period
15.5% (CI 95% 10.3-22.1%) of women took appropriate dosage.
86% (CI 95% 73-86%) were planned pregnancies
41% (CI 95% 33-50%) of women did not know benefits of folic acid
Information campaigns to care providers and general population
133
Reviews by Spanish Authors
In recent years, some authors have published articles referring to folic acid
supplementation and the need to strengthen policies to improve intake. Four
references should be mentioned: Madueño and Muñoz (2001)(15), Capitán and
Carrera (2001)(16) and Carrera (2003)(17), Martinez-Frias (2007)18) All of them stress
the need to improve information to care providers and the general population.
Aranceta et al (2001)(19) and Ortega et al (2001)(20) carried out reviews at an
international level.
Health Education Initiatives
Since 2001 pharmaceutical companies and Public Health departments have carried
out health campaigns to inform health professionals about the recommendations for
periconceptional folic acid supplementation (Madrid, Valencia, Navarra, Murcia,
Extremadura and the Basque Country).
A new official centre was created in 2002 at the Carlos III Institute which is a part of
Ministry of Health, “Centro de Investigación de Anomalías Congénitas (CIAC)”,
connected to the ECEMC project (Estudio Colaborativo Español de Malformaciones
Congenitas). Some pamphlets for the general population about prevention of NTDs
with folic acid are available from the web(21).
In some autonomous communities the Public Health Departments have been making
“records” about recommendations (internal papers, webs) for doctors and nurses
and also local campaigns and leaflets for general people.
Coll et al (2004)(14)
Retrospective
1000 consecutive women who delivered in Hospital in Barcelona
2000
6.9% of women took appropriate dosage
85.7% of women had not been informed by care providers
50.6% were aware of benefits of folic acid.
Information about folic acid should be given in primary care and preconceptional counselling
Martinez-Frias et al
2007 8)
Retrospective
16,761 recently delivered mothers of non-malformed infants
17.% took FA prior to conception.
71% took FA once pregnant. Most of them took high dose (=/>4mg)
134
Proportion of pregnancies that are planned There are no reliable national figures about the number that are planned. A survey
in Barcelona from 1994 to 2006 found that between half and two thirds of
pregnancies surveyed were planned.
Laws Regarding Termination of Pregnancy
Termination of pregnancy in Spain is allowed up to 22 weeks of gestation if the fetus
is expected to be born with severe physical or intellectual defects (unspecified). Two
doctors must sign that any of those indications is present. This gestational age limit
was confirmed in 2004 by the Spanish Governmental Authorities.
Authorised compounds of Folic Acid
There are a total of 23 proprietary preparations with folic acid (3 with folic acid only,
and the rest in combination with other vitamins or minerals), containing
varying dosages between 75 micrograms and 5 milligrams of folic acid. The price per
day ranges from 0.04 to 0.13 Є and is 60% subsidized by the Health System. A
further 18 folinic acid compounds (calcic folinate or levofolinate) are also licensed
for sale, and their use during pregnancy is accepted (even with the higher dosages,
varying between 1.08 and 350 milligrams). The price for these is 9 times higher than
for folic acid and is subsidized by more than 60% by the Health System. In 1999 the
Basque Society of Gynaecology together with the Health Department issued
recommendations about periconceptional intake of folic acid and also discouraged
gynaecologists from prescribing levofolinic acid. It would be advisable to monitor the
use of levofolinic acid for periconceptional care.
References 1. Grupo Institucional. Ministerio de Educación y Cultura y Ministerio de Interior.
Nutrición Saludable y Prevención de los Trastornos Alimentarios. Jul 2003. Available from http: www.msc.es/proteccionSalud/adolescencia/Juven/prevenir/nutricion
2. Dirección de Salud Pública. Ministerio de Sanidad y Consumo. (2001) Recomendaciones sobre suplementación con ácido fólico para la prevención de defectos del tubo neural. Inf Ter Sist Nac Salud; 25: 66-7.
135
3. Dirección de Salud Pública. Educación para la salud. Salud de la mujer. May 2004. Available from: http://www.euskadi.net/sanidad/publicaciones/eps_c.htm.
4. Aranceta J, Pérez C, Eguileor I, Marzana I, González de Galdeano L, Saenz de Buruaga J (1994). Encuesta de nutrición de la Comunidad Autónoma del País Vasco.Tendencias de consumo alimentario, indicadores bioquímicos y estado nutricional de la población adulta. Vitoria: Departamento de Sanidad. Gobierno Vasco.
5. Vioque, J, Quiles J, García de la Hera, M, Guillén M, Ponce E, Muñoz, P (2000). Ingestión de ácido fólico y factores asociados a mujeres adultas de 15 a 44 años de la Comunidad Valenciana. Med Clin(Bar), 11: 414-416.
6. Ballesteros G, Muñoz P, Lopez ME, De Miguel JR (1999). Folates y vitamin B12 en mujeres gestantes. Prog Obstet Ginecol, 42(8): 543-557.
7. García R, Serra L, Sabater G et al (2002). Distribución en el suero de concentraciones de vitamina C, ácido fólico y vitamina B12 en una muestra representativa de la población adulta de Cataluña. Med Clinic(Bar), 9, 118 (4): 135-141.
8. Martinez-Frias y Grupo de trabajo del ECEMC, Adecuacion de las dosis de acido folico en la prevencion de defectos congenitos, MedClin (Barc) 2007, 128(16)609-616.
9. Gilbert MJ, Juncosa N, Martín I (2000). Prevención Primaria de los defectos del tubo neural en la población atendida en un hospital de referencia. Prog Obstet Ginecol, 43: 13-20.
10. Martínez-Frías ML, Rodriquez Pinilla, E and Bermejo, E (2003). Análisis de la situación en España sobre el consumo de ácido fólico/folinato cálcico para la prevención de defectos congénitos. Med Clin(Barc)121(20):772-775.
11. Garcia MM, González, AI and Jiménez R ( 2003). Profilaxis de los defectos del tubo neural con folatos en las mujeres gestantes del Area 10 de Madrid. Atención Primaria, 31, 2: 98-103.
12. Gutierrez JI, Perez F, Tamparillas M and Calvo MT (2003). Prevención de los defectos del tubo nerural mediante la suplementación adecuada con ácido fólico. AtenFarm, 5 (2):84-92.
13. Pérez-Vázquez A, Vidal R, Castro M and Aulet A (2003) Prevalencia del uso preconcepcional del ácido fólico en el norte de Pontevedra. Atención Primaria, 32 (7).
14. Coll O, Pisa S, Palacio M, Quinto L et Cararach V (2004). Awareness of the use of folic acid to prevent neural tube defects in Mediterranean area. Eur J Obstet Gynecol ReprodBiol, 10, 115 (2):173-77.
15. Madueño, A and Muñoz-Cruzado, M. (2001) Variabilidad clínica en la indicación de folatos a la embarazada. Medifam, 11, 6:87-88.
16. Capitán, M and Carrera R (2001). La consulta preconcepcional en Atención Primaria. Evaluación de la futura gestante. Medifam, 4, 11: 207-215.
17. Carrera, JM (2003). Prevención primaria de los defectos del tubo neural. MedClin (Barc) 121(20):782-784.
18. Martinez-Frias (2006) Lancet Vol 367, 2057 19. Aranceta J, Serra-Majem Ll, Pérez-Rodrigo C, Llopis J, Mataix J, Ribas L,
Tojo R and Tur JA (2001). Vitamins in Spanish food patterns: the eVe study. Public Health Nutr, Vol 4, No 6A, pp 1317-1323.
20. Ortega RM, Mean MC, Faci M, Santana FJ and Serra-Majem Ll (2001). Vitamin status in different groups of the Spanish population: a metaanalysis of
136
national studies performed between 1990-1999. Public Health Nutr, Vol 4, No 6A, pp 1325-1329.
21. Centro de Investigación de Anomalías Congénitas (CIAC). Octubre 2002. Available from: http://www.iier.isciii.es/er/html/er_preve.html.
Spain (Basque Country, Barcelona and Madrid): Total and Livebirth Prevalence Rates for Neural Tube Defects (all 3 registries together)
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Spain (Basque Country, Barcelona and Madrid): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Basque Country Total prevalence Barcelona Total prevalence MadridLivebirth prevalence Basque Country Livebirth prevalence Barcelona Livebirth prevalence Madrid
137
Spain (Basque Country, Barcelona and Madrid): Total and Livebirth Prevalence Rates for Spina Bifida (all 3 registries together)
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Spain (Basque Country, Barcelona and Madrid): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Basque Country Total prevalence Barcelona Total prevalence MadridLivebirth prevalence Basque Country Livebirth prevalence Barcelona Livebirth prevalence Madrid
138
Spain (Basque Country, Barcelona and Madrid): Total and Livebirth Prevalence Rates for Anencephaly (all 3 registries together)
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Spain (Basque Country, Barcelona and Madrid): Total Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Basque Country Total prevalence Barcelona Total prevalence Madrid
139
Report on Periconceptional Folic Acid Supplementation For Sweden Göran Annerén and Birgitta Ollars
Folic Acid Supplementation Policy The National Board of Health and Welfare issued recommendations regarding
dietary folate and periconceptional folic acid supplementation in 19961 and again in
2001.2 Women who are planning a pregnancy or who may become pregnant are
recommended to have a total intake of at least 400 µg of folate per day. Since an
intake of 400 µg through the diet is unlikely to be achieved by many women, the
official recommendation is to take a folic acid supplement of 400 µg per day. The
supplementation should begin one month prior to conception and continue until the
end of the first trimester.
Women who have previously had a foetus with a neural tube defect (NTD), women
who themselves or whose partner have a NTD or a close relative with a NTD,
women with an increased need for folic acid due to disease or medication, such as
anti-epileptic medication, are recommended to take 4-5 mg of folic acid supplement
per day. The supplementation should begin one month prior to conception and
continue until 2-3 months of gestation. This recommendation for women at high risk
was issued in 1991.3
In September 2007, The Board of the National Food Administration, in Sweden,
made the strategic decision to distribute folic acid supplements free of charge to
women in the age range 18-45 years, plus complementary information measures.
The decision involves, in the first instance, activities during a five-year period. The
first year will be taken up with planning and detailed decisions concerning the
activities. Thereafter, all women in the age range 18-45 years will be sent an annual
letter with information on the link between folic acid and the risk of spina bifida, plus
the offer of free folic acid tablets. The results will be continuously assessed.
Food Fortification Policy The Board of National Food Administration reached a decision in 2007 that
140
compulsory enrichment would be inappropriate in view of the uncertainty regarding
the increased risk of cancer due to high intake of folic acid. The National Food
Administration will continue to monitor the scientific discussion on folic acid in the
future. The European Food Safety Authority (EFSA) together with the National Food
Administration will arrange a scientific meeting on the question of folic acid and
cancer in Sweden in the beginning of 2008.
Health Education Initiatives No official Health Education Initiative has been performed in Sweden to inform
women about the role of folic acid in reducing the risk for neural tube defects.
However, this is about to change since the 2007 decision by the Board of the
National Food Administration means that all women in the age range 18-45 years will
be sent an annual letter with information on the link between folic acid and the risk of
spina bifida, plus the offer of free folic acid tablets. Knowledge and Uptake about Folic Acid
To our knowledge no national epidemiological studies have been conducted. About
8% of pregnant women used periconceptional supplementation in 1997 but this
figure is probably an under estimate.4
Dietary studies in Sweden indicate that only a small group of women of childbearing
age achieve the daily recommended intake of 400 micrograms of folic acid or dietary
equivalent at present.
Proportion of Pregnancies that are Planned
There is little knowledge in Sweden about the proportion of pregnancies that are
planned. Probably the situation in Sweden is similar to that in Norway where they
reported that between 50 and 75% of all pregnancies were planned.
Laws Regarding Termination of Pregnancy Induced abortion is legal at a woman’s request up to 18 completed weeks of
gestation. Induced abortion is legal on specified medical and social indications
between 18 and 22 completed weeks, and the decision is made by an ethical
committee at the National Board of Health and Welfare.
141
References
1. National Board of Health and Welfare 1996, Aktuellt i folsyra frågan.
http://www.sos.se/SOS/PUBL/MEDBLAD/Mb9608.htm
2. National Board of Health and Welfare 2001, Folsyra i samband med
graviditet. http://www.sos.se/SOS/PUBL/MEDBLAD/Mb0101.htm
3. Annerén 1991, Erbjud folatbehandling till kvinnor med ökad risk att föda barn
med neuralrörsdefekt. Läkartidningen 1991;88:4110
4. Ericson 2001, Use of Multivitamins and Folic Acid in Early Pregnancy and
Multiple Births in Sweden. Twin research, 2001;Vol 4;2:63-66
142
Report on Periconceptional Folic Acid Supplementation for Switzerland Dr Marie-Claude Addor and Monika Eichholzer
Switzerland is a federal country comprising 26 cantons. Most responsibilities in the
health field are vested in the Cantonal Public Health Services. On the federal level,
there is a Federal Office of Public Health whose guidelines now have a large
audience and are used as the legal basis.
Folic Acid Supplementation Policy In the early 1990s, the Public Health Officer for the canton of Vaud, at the request of
the University Department of Gynecology and Obstetrics, asked the Federal Office of
Public Health to support the idea of a national recommendation concerning folic acid
and the prevention of neural tube defects (NTD).
The recommendations for primary prevention, issued in 2002, are as follows:
• 0.4 mg folic acid supplementation (with or without other vitamins) should be
taken daily from four weeks before conception until twelve weeks after.
• All women of child bearing age without safe contraception should consume a
folate rich diet (fresh fruits and vegetables, whole grain products and fortified
food eg cereals and breakfast beverages).
• Women who have had a previous pregnancy affected by a neural tube defect
are advised to take the following supplements periconceptionally:
4-5 mg folic acid daily, monopreparation (Folvite, Ac. Folicum,
Foli-Rivo)
polyvitamins = 0.4-1 mg folic acid (vit A ≤ 8000 Ul)
Food Fortification Policy Voluntary fortification of food with folic acid is legal, but mandatory fortification has
not been introduced.
In 1997, Wiederkehr et al submitted to the Swiss representative assembly a proposal
for the mandatory fortification of flour with folic acid for the prevention of neural tube
defects. In 2000, the Federal Office of Public Health began studying the folate
143
situation in Switzerland (4)and in 2002 a working group of the Swiss Nutrition
Council submitted a report for the Federal Government with scientific
recommendations(5). They recommended that flour should be fortified on a
mandatory basis by 3 mg folic acid and 10 micrograms of vitamin B12 per kg of flour
in order to obtain a supplementary daily intake of folic acid of 275 micrograms and
about 1 microgram of B12 per day and said this was the most efficacious, sure and
economic way to prevent NTD. This recommendation was supported by the Swiss
Nutrition Council but not by the Federal Office of Public Health.
A further report was issued in November 2006 saying that there is no legal basis for
mandatory fortification in the Swiss law (6)
Health Education Initiatives In 2005, a working group of the Federal Office of Public Health prepared a booklet
and a leaflet for women in childbearing age. Some booklets, edited by pharmacists
“vitamin info” will be available in waiting rooms of gynaecologists in 2008.
Uptake and Knowledge of Folic Acid. According to market research, awareness of folic acid in the population increased
from 38% in 1999 to 58% in 2003. Jans-Ruggli and Baerlocher looked at a sample
of 505 pregnant women in three hospitals in Eastern Switzerland between
September 2002 and October 2003. (7) They found that 97.5% of women in their
study women took a folic acid supplement during pregnancy, but only 37% took it at
the correct time to prevent NTDs. Women of Western European origin were better
informed about folic acid then were women from Eastern countries (Balcan and
Turkey). Older women were better informed than younger women.
In Switzerland, the daily dietary intake of folate has been estimated to be 275 μg or
less.
144
Proportion of Pregnancies that are Planned The percentage of pregnancies that are planned in Switzerland is thought to be very
low, and there are very few “preconceptional consultations”. However, in the Jans-
Ruggli, Baerlocher study, 80% of the pregnancies were said to be planned.
Laws Regarding Termination of Pregnancy According to the Swiss penal code, there is no gestational age limit for termination of
pregnancy. However, in practice it is performed until the 24th week of gestation.
References 1. Tönz O., Lüthy J., Raunhardt O (1996), Folsäure zur Verhütung von
Neuralrohrdefekten. Schweiz Med Wochenschr, Vol 126, pp 177-187.
2. Tönz O., Lüthy J (1996), Folsäure zur primären Verhütung von
Neuralrohrdefekten Bulletin des Médecins Suisses, Vol 77, No 14, pp 569-572
3. Tonz O. Das Praventive Potential der Folsaure. In: Eichholzer M, Camenzinid-
Frey E, Matzke A et al. Funfter Schweizerischer Ernahrungsbericht. Bern:
Bundesamt fur Gesundheit, 2005.
4. Eichholzer M., Lüthy J., Moser U., Stähelin H.B., Gutzwiller F (2002), Sicherheitsaspekte der Folsäure für die Gesamtbevölkerung. Praxis, Vol 91,
pp 7-16
5. Baerlocher K., Eichholzer M., Lüthy J., Moser U., Tönz O.: Acide folique:
Rapport d'experts de la commission fédérale d'alimentation sur la prophylaxie
des anomalies du tube neural. Office fédéral de la santé publique, Berne
2002, 73p.
6. November 2006: (www.bad.admin.ch (Themen/Ernahrung, Lebensmittel und
Ernahrung/Ernahrung/Ernahrung von A bis Z/Folsaure)
7. Sandra Jans-Ruggli, Kurt Baerlocher, Swiss Federal Office of Public Health,
5th Swiss Report of Nutrition, Knowledge of pregnant women about folic acid
and folic acid status in mothers: Frequent intake of folic acid supplements, but
insufficient prevention of NRD, Berne November 2005.
145
Switzerland (Vaud): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Switzerland (Vaud): Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
146
Switzerland (Vaud): Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
147
Report on Periconceptional Folic Acid Supplementation for Ukraine Dr Natalya Zymak-Zakutnya
Folic Acid Supplementation Policy In Ukraine an official policy regarding increasing folate in the diet was introduced on
December 28, 2002. The policy advises to take 0.4 mg in 3 months before
conception till 16 weeks of pregnancy1.
This is a Ministry of Health Care of Ukraine Order No. 503 “On Improvement of
Outpatient Obstetric-gynecologic Aid in Ukraine” (28.12.2002).
Food Fortification Policy There is no official food fortification policy. There are imported fortified cereals and
malted drinks, but not widely available. Fortified breads are not readily available.
Health Education Initiatives
No official Department of Health Care Promotion campaigns have been undertaken
but GPs, gynecologists, midwives organised antenatal courses to inform women of
the benefits of folic acid. The official dietary policy mentioned above was aimed to
inform and educate health professionals.
A number of initiatives were launched by non-profit organizations, e.g.:
• Educational project "One way to life's harmony - without birth defects - is folic
acid", November 3, 2001 (Rivne, Ukraine), held by Ukrainian - American Birth
Defects Program (UABDP), NGO Ukrainian Alliance for the Prevention of
Birth Defects and political consolidation “Women for Future”;
• International conference “Fortification of food with vitamin B9 with the aim of
neural tube defects prevention”, November 27-29, 2006 (Kyiv).
• 1st Central and Eastern European Summit on Preconception Health and
Prevention of Birth Defects, August 27-30, 2008 (Budapest) - analysis and
discussion of the promotion of women’s health before, during and beyond
pregnancy, and the role of preconception health and health care in the
prevention of birth defects in the Central and Eastern European region.
Ukrainian participants presented results of a folic acid related survey: Survey
of Pre-conception Health and Birth Defects Prevention Knowledge and
Attitudes in Ukraine1.
148
Folic Acid Awareness and Uptake A study regarding folic acid and pregnancy risk factors awareness in Ukrainian
mothers was undertaken in Jan- May 2008. The results were presented at 1st
Central and Eastern European Summit on Preconception Health and Prevention of
Birth Defects, August 27-30, 2008, Budapest2. The aim was to assess knowledge
and attitudes regarding pre-conception health and birth defects prevention in
Ukraine. This pilot survey was held in six heterogenous regions (northwest, Rivne
and Volyn oblasts; west, Transcarpathia oblast; south, Kherson oblast; and central-
west, Khmelnytsky and Cherkasy oblasts).
A questionnaire was designed by OMNI-Net partners with consideration to previous
surveys conducted by the March of Dimes and other agencies. Pregnant women
seeking family planning or medical genetic services were asked to volunteer
anonymously information about their ethnicity, health, previous pregnancies and
negative pregnancy outcome risk factors. Information was recorded by health care
personnel.
Proportion of pregnancies which are planned No information available.
Laws Regarding Termination of Pregnancy Termination of pregnancy is legal and performed by a physician when:
1) a pregnancy poses danger to health or life of a pregnant women;
2) prenatal diagnosis or other medical evidence indicates high probability of serious
and irreversible damage to a fetus or it is an untreatable life-threatening disease;
3) there is a plausible suspicion the pregnancy has arisen from a prohibited act.
Gestational age limit – from January 2007 – before 22 weeks3.
References: 1. Order No. 503 “On Improvement of Outpatient Obstetric-gynecologic Aid in
Ukraine”, Ministry of Health Care of Ukraine, December, 28, 2002.
2. Patskun E., Kalynka S., Onishchenko S., Semenenko O., Yevtushok L.,
Zymak-Zakutnya N. (2008). Survey of Pre-conception Health and Birth
Defects Prevention: Knowledge and Attitudes in Ukraine. – Program &
149
Abstract Book: 1st Central and Eastern European Summit on Preconception
Health and Prevention of Birth Defects, p. 95, August 2008, Budapest.
3. Decree No.144 “On Implementation of Article 281 of Civil Code of Ukraine”,
Cabinet of Ministers of Ukraine, February, 15, 2006.
Ukraine: Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
Ukraine: Total and Livebirth Prevalence Rates for Spina Bifida
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
150
Ukraine: Total and Livebirth Prevalence Rates for Anencephaly
0
5
10
15
20
25
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0,00
0 bi
rths
Total prevalence Livebirth prevalence
151
Report on Periconceptional Folic Acid Supplementation for the United Kingdom Dr Grace Edwards and Lenore Abramsky
Folic Acid Supplementation Policy
The Medical Research Council Vitamin Study confirmed the role of periconceptional
folic acid supplementation in reducing the risk of a fetal neural tube defect. 1 As a
result, in 1992 the Department of Health in conjunction with the Scottish Office, the
Welsh Office and the Northern Ireland office produced a report recommending that
folic acid supplementation should be taken by all women contemplating pregnancy.
The report recommended that all women take 400 µg of folic acid per day when
planning a pregnancy. Women who had had a baby with a previous neural tube
defect were advised to take 5 mg per day before conception and until 12 weeks of
pregnancy. 2 These recommendations are still in place.
Food Fortification Policy Mandatory fortification of flour in the United Kingdom has been recommended by the
Food Standards Agency but not yet implemented. It is expected to be implemented
in 2008. Most breakfast cereals have been voluntarily fortified for many years with
vitamins such as B vitamins, including folic acid, and minerals such as iron. There is
no standardized amount and there are varying levels of fortification with folic acid.
Health Education Initiatives
In 1995 a three year UK campaign led by the Health Education Authority (HEA) was
launched to improve folate status awareness in women of child bearing age. This
campaign highlighted ways of improving folate status before conception and up to 12
weeks of pregnancy by increasing folic acid intake from foods and supplements.
This was a large and expensive campaign with advertisements on television, in
newspaper, magazines and professional journals. Although the campaign raised
awareness in women from 9% in 1995 to 68% in 1998, only 38% of women surveyed
in 1998 took folic acid around the time of conception. 3
It should be noted that Northern Ireland was not covered by the television advertising
campaign launched by the HEA in 1995. However, a Northern Ireland television
152
advertising campaign was broadcast as part of a public information initiative
developed by the Health Promotion Agency for Northern Ireland and launched in
1998.
Knowledge and Uptake of Folic Acid Numerous studies have been undertaken in the UK and Ireland and all have shown
that while the majority of women have now heard of folic acid and know something
about its protective effect, fewer than half of them take it prior to conception. Most of
the studies have looked at the association of demographic and lifestyle variables
with uptake and have found that uptake is lower among young women, smokers,
those with less formal education, of lower social class, and from ethnic minorities. 4-9
Some work has been undertaken in the United Kingdom to measure the changes in
dietary folate consumption. 10,11 Murphy et al found that dietary folate consumption
had increased by 1.6% per annum in Scotland and 1.4% in England from 1980 to
1996. This increase was thought to have been linked with the introduction of folate
fortification of cereals.
In Northern Ireland anecdotal evidence from antenatal clinics indicates an increase
in uptake of folic acid supplements.
Proportion of Pregnancies which are Planned
A study by While found that up to one live birth out of every three was unplanned. 12
These findings were supported by research in Merseyside, England where forty
percent of women reported that their pregnancies were unplanned 13 and by research
in other parts of Britain 6
Laws Regarding Termination of Pregnancy
Under the 1967 Abortion Act (amended in 1990) abortion is legal in England,
Scotland and Wales at gestational age up to 24 weeks provided that two doctors
certify that a woman’s mental or physical health (or that of her children) is at greater
risk if she continues with the pregnancy than if she has a termination. At the time of
153
writing (October 2007), the UK parliament is considering the possibility of removing
the need for two doctors to certify that the criteria for permitting a termination are met
and is also considering the possibility of lowering the gestational age limit to 22
weeks. There is no gestational age limit for termination of pregnancy because of
serious fetal abnormality or because there is a risk of permanent injury to a woman’s
health or life. The 1967 Abortion act does not apply in Northern Ireland.
References 1. MRC Vitamin Study Research Group, Prevention of Neural Tube Defects:
Results of the MRC Vitamin Research Study, Lancet, (1991), 338, 131-137
2. Department of Health, Folic Acid and Neural Tube Defects,:Guidelines on
Prevention, Department of Health Directive PL/CMO (1992) 18 London HMSO
3. Health Education Authority Folic Acid Update, 1998 HEA, London, UK
4. McGovern E, Moss H, Grewall G, Taylor A, Bjornsson S, Pell J, Factors
affecting the use of folic acid supplements in pregnant women in Glasgow,
British Journal of Medical Practice, (1997) 47; 635-7
5. Neill AM, Laing RJ, Perez P, Spencer PJ, The Folic Acid Campaign: has the
message got through? A questionnaire study. J Obstet Gynaecol, 1999
Jan;19(1):22-5.
6. Sens S, Manzoor A, Deviasumathy M, Newton C , Maternal knowledge,
attitude and practice regarding folic acid intake regarding the periconceptional
period, Public Health Nutrition, 2001, August 4, 909-912
7. Langley-Evans SC, Langley-Evans AJ. Use of folic acid supplements in the
first trimester of pregnancy. J R Soc Health, 2002 Sep;122(3):181-6.
8. Ward M, Hutton J, McDonnel R, Bachir N, Scallan E, O’Leary M, Hoey J,
Doyle A, Delany V, Sayers G, Folic acid supplements to prevent neural tube
defects: trends in East of Ireland 1996-2002. Ir Med J. 2004 Oct;97(9):274-6.
9. Relton CL, Hammal DM, Rankin J, Parker L, Folic acid supplementation and
social deprivation. Public Health Nutr. 2005 May;8(3):338-40.
10. Mathews F, Udkin P, Neil A (1998), Folates in the Periconceptional Period,
Are Women Getting Enough?, British Journal of Obstetrics & Gynecology, Vol
105, pp 954-959
11. Murphy M, Whiteman D, Stone D, Botting B, Schorah C, Wild J, (2000),
Dietary Folate and the Prevalence of Neural Tube Defects in the British Isles:
154
The past two decades, British Journal of Obstetrics & Gynecology, Vol 107,
No 7, pp 885-889
12. While A E (1990), The incidence of unplanned and unwanted pregnancies in
live births in health visitors’ records, Child: Care, Health and Development
1990, 16; 219-226
13. Edwards G A, Public Perceptions about how maternal diet, drinking habits
and activities during pregnancy might affect the wellbeing of the fetus, 2001
Unpublished PhD thesis, University of Liverpool
Thanks to Margaret Slane of the Health Promotion Agency in Northern Ireland and
Margaret Boyle, Senior Medical Officer, Department of Health, Social Services and
Personal Safety Northern Ireland for their input about the situation in Northern
Ireland.
UK (North Thames, Wales, Thames Valley, Wessex, Trent and Northern Region): Total and Livebirth Prevalence Rates for Neural Tube Defects (all 6 registries together)
0
2
4
6
8
10
12
14
16
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
155
UK (North Thames, Wales, Thames Valley): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
5
10
15
20
25
30
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence NW Thames Total prevalence Wales Total prevalence Thames ValleyLive birth prevalence NW Thames Livebirth prevalence Wales Livebirth prevalence Thames Valley
UK (Wessex, Trent and Northern Region): Total and Livebirth Prevalence Rates for Neural Tube Defects
0
2
4
6
8
10
12
14
16
18
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Wessex Livebirth prevalence Trent Livebirth prevalence Northern RegionLivebirth prevalence Wessex Total prevalence Trent Total prevalence Northern Region
156
UK (North Thames, Wales, Thames Valley, Wessex, Trent and Northern Region): Total and Livebirth Prevalence Rates for Spina Bifida (all 6 registries together)
0
1
2
3
4
5
6
7
8
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
UK (North Thames, Wales, Thames Valley): Total and Livebirth Prevalence Rates for Spina Bifida
0
2
4
6
8
10
12
14
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence NW Thames Total prevalence Wales Total prevalence Thames ValleyLive birth prevalence NW Thames Livebirth prevalence Wales Livebirth prevalence Thames Valley
157
UK (Wessex, Trent, Northern Region): Total and Livebirth Prevalence Rates for Spina Bifida
0
1
2
3
4
5
6
7
8
9
10
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Wessex (GB) Trent (GB) Northern Region (GB) Livebirth prevalence Wessex Livebirth prevalence Trent Livebirth prevalence Northern Region
UK (North Thames, Wales, Thames Valley, Wessex, Trent and Northern Region): Total and Livebirth Prevalence Rates for Anencephaly (all 6 registries together)
0
1
2
3
4
5
6
7
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
Total prevalence Livebirth prevalence
158
UK (North Thames, Wales, Thames Valley, Wessex, Trent and Northern Region): Total Prevalence Rates for Anencephaly
0
2
4
6
8
10
12
14
1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
Prev
alen
ce p
er 1
0.00
0 bi
rths
N W Thames (UK) Wales (GB) Thames Valley (GB) Wessex (GB) Trent (GB) Northern Region (GB)